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The "Protein Abundances Across Organisms" database (PaxDb) is an integrative metaresource dedicated to protein abundance levels, in tissue-specific or whole-organism proteomes. PaxDb focuses on computing best-estimate abundances for proteins in normal/healthy contexts and expresses abundance values for each protein in "parts per million" in relation to all other protein molecules in the cell. The uniform data reprocessing, quality scoring, and integrated orthology relations have made PaxDb one of the preferred tools for comparisons between individual datasets, tissues, or organisms. In describing the latest version 5.0 of PaxDb, we particularly emphasize the data integration from various types of raw data and how we expanded the number of organisms and tissue groups as well as the proteome coverage. The current collection of PaxDb includes 831 original datasets from 170 species, including 22 Archaea, 81 Bacteria, and 67 Eukaryota. Apart from detailing the data update, we also present a comparative analysis of the human proteome subset of PaxDb against the two most widely used human proteome data resources: Human Protein Atlas and Genotype-Tissue Expression. Lastly, through our protein abundance data, we reveal an evolutionary trend in the usage of sulfur-containing amino acids in the proteomes of Fungi.
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Liver cancer is one of the malignancies with high mortality rates worldwide, and its timely detection and accurate diagnosis are crucial for improving patient prognosis. To address the limitations of traditional image segmentation techniques and the U-Net network in capturing fine image features, this study proposes an improved model based on the U-Net architecture, named RHEU-Net. By replacing traditional convolution modules in the encoder and decoder with improved residual modules, the network's feature extraction capabilities and gradient stability are enhanced. A Hybrid Gated Attention (HGA) module is integrated before the skip connections, enabling the parallel processing of channel and spatial attentions, optimizing the feature fusion strategy, and effectively replenishing image details. A Multi-Scale Feature Enhancement (MSFE) layer is introduced at the bottleneck, utilizing multi-scale feature extraction technology to further enhance the expression of receptive fields and contextual information, improving the overall feature representation effect. Testing on the LiTS2017 dataset demonstrated that RHEU-Net achieved Dice scores of 95.72% for liver segmentation and 70.19% for tumor segmentation. These results validate the effectiveness of RHEU-Net and underscore its potential for clinical application.
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Procesamiento de Imagen Asistido por Computador , Neoplasias Hepáticas , Redes Neurales de la Computación , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Hígado/diagnóstico por imagen , Hígado/patologíaRESUMEN
To solve the small sample size (SSS) problem in the classification of hyperspectral image, a novel classification method based on diverse density and sparse representation (NCM_DDSR) is proposed. In the proposed method, the dictionary atoms, which learned from the diverse density model, are used to solve the noise interference problems of spectral features, and an improved matching pursuit model is presented to obtain the sparse coefficients. Airborne hyperspectral data collected by the push-broom hyperspectral imager (PHI) and the airborne visible/infrared imaging spectrometer (AVIRIS) are applied to evaluate the performance of the proposed classification method. Results illuminate that the overall accuracies of the proposed model for classification of PHI and AVIRIS images are up to 91.59% and 92.83% respectively. In addition, the kappa coefficients are up to 0.897 and 0.91.
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Protein quantification at proteome-wide scale is an important aim, enabling insights into fundamental cellular biology and serving to constrain experiments and theoretical models. While proteome-wide quantification is not yet fully routine, many datasets approaching proteome-wide coverage are becoming available through biophysical and MS techniques. Data of this type can be accessed via a variety of sources, including publication supplements and online data repositories. However, access to the data is still fragmentary, and comparisons across experiments and organisms are not straightforward. Here, we describe recent updates to our database resource "PaxDb" (Protein Abundances Across Organisms). PaxDb focuses on protein abundance information at proteome-wide scope, irrespective of the underlying measurement technique. Quantification data is reprocessed, unified, and quality-scored, and then integrated to build a meta-resource. PaxDb also allows evolutionary comparisons through precomputed gene orthology relations. Recently, we have expanded the scope of the database to include cell-line samples, and more systematically scan the literature for suitable datasets. We report that a significant fraction of published experiments cannot readily be accessed and/or parsed for quantitative information, requiring additional steps and efforts. The current update brings PaxDb to 414 datasets in 53 organisms, with (semi-) quantitative abundance information covering more than 300,000 proteins.
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Bases de Datos de Proteínas , Proteoma/análisis , Proteómica/métodos , Programas Informáticos , Animales , HumanosRESUMEN
Objective: The objective was to explore the impact of WeChat follow-up management on the psychological distress, care burden, and quality of life of parents of infants with bronchopulmonary dysplasia (BPD) receiving in-home care. Methods: This was a retrospective cohort study. A total of 101 parents of infants with BPD who were followed up from January 2016 to January 2022 were included in this study. According to different follow-up methods, these patients were classified into the WeChat group and the routine group. The Depression, Anxiety, and Stress Scale-21 (DASS-21), Zarit Caregiver Burden Interview (ZBI), and WHOQOL-BREF were used. The data on the psychological distress, care burden, and quality of life of the parents in the two groups were analyzed and compared at discharge and at the 3-month follow-up. Results: There was no significant difference in the DASS-21 and ZBI scores at discharge between the parents in the two groups. During the 3-month follow-up, the scores of the DASS-21 anxiety and stress subscale and the ZBI of parents in the WeChat group were significantly lower than those of parents in the routine group (P < 0.05); however, there was no significant difference in the depression subscale score between the two groups (P > 0.05). A comparison of the WHOQOL-BREF score between the two groups showed that the total quality of life score in the WeChat group was significantly higher than that in the routine group (P < 0.05). The scores of the psychological and social relationship fields in the WeChat group were significantly higher than those in the routine group (P < 0.05). The incidence of adverse events during follow-up was significantly lower in the WeChat group than in the routine group (P < 0.05). Conclusion: WeChat follow-up management is helpful to decrease the anxiety and stress, reduce the care burden, and improve the quality of life of parents of infants with BPD receiving in-home care.
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Six phosphorescence-emitting metal-organic mononuclear Cu(I) complexes, namely four quinoline-containing three-coordinate Cu(I) complexes and two N-heterocyclic carbene-containing four-coordinate Cu(I) complexes, have been successfully developed and fully characterized. All these Cu(I) complexes include the same bis(2-diphenylphosphinophenyl)ether bidentate auxiliary ligand. Significantly, four-coordinate Cu(I) complexes 1 and 2 display typical aggregation-induced emission phenomena. Their solid samples of luminogenic complexes 1-6 emit a variety of different phosphorescence. Furthermore, solid-state phosphorescence of these Cu(I) complexes can be effectively manipulated by external mechanical force. Remarkably, luminophores 1, 2 and 5 exhibit blue-shifted mechanoluminochromism responses, while luminophores 3, 4 and 6 present red-shifted mechanoluminochromism characteristics. All of the observed mechano-responsive phosphorescence changes of solids 1-6 are reversible by the method of solvent fuming. Powder X-ray diffraction results confirm that the reversible mechanically induced phosphorescence changes of complexes 1-6 are due to the mutual transformation of ordered crystalline and metastable amorphous states.
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Band gap tuning in mixed-halide perovskites enables efficient multijunction solar cells and LEDs. However, these wide band gap perovskites, which contain a mixture of iodide and bromide ions, are known to phase segregate under illumination, introducing voltage losses that limit stability. Previous studies have employed inorganic perovskites, halide alloys, and grain/interface passivation to minimize halide segregation, yet photostability can be further advanced. By focusing on the role of halide vacancies in anion migration, one expects to be able to erect local barriers to ion migration. To achieve this, we employ a 3D "hollow" perovskite structure, wherein a molecule that is otherwise too large for the perovskite lattice is incorporated. The amount of hollowing agent, ethane-1,2-diammonium dihydroiodide (EDA), varies the density of the hollow sites. Photoluminescence measurements reveal that 1% EDA in the perovskite bulk can stabilize a 40% bromine mixed-halide perovskite at 1 sun illumination intensity. These, along with capacitance-frequency measurements, suggest that hollow sites limit the mobility of the halide vacancies.
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The optoelectronic properties of metal-halide perovskites (MHPs) are affected by lattice fluctuations. Using ultrafast pump-probe spectroscopy, we demonstrate that in state-of-the-art mixed-cation MHPs ultrafast photo-induced bandgap narrowing occurs with a linear to super-linear dependence on the excited carrier density ranging from 1017 cm-3 to above 1018 cm-3. Time-domain terahertz spectroscopy reveals carrier localization increases with carrier density. Both observations, the anomalous dependence of the bandgap narrowing and the increased carrier localization can be rationalized by photo-induced lattice fluctuations. The magnitude of the photo-induced lattice fluctuations depends on the intrinsic instability of the MHP lattice. Our findings provide insight into ultrafast processes in MHPs following photoexcitation and thus help to develop a concise picture of the ultrafast photophysics of this important class of emerging semiconductors.
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Interfaces in metal halide perovskite (MHP) solar cells cause carrier recombination and thereby reduce their power conversion efficiency. Here, ultrafast (picosecond to nanosecond) transient reflection (TR) spectroscopy has been used to probe interfacial carrier dynamics in thin films of the reference MHP MAPbI3 and state-of-the-art (Cs0.15MA0.15FA0.70)Pb(Br0.20I0.80)3 (CsFAMA). First, MAPbI3 films in contact with fullerene-based charge extraction layers (CTLs) in the presence and absence of LiF used as an interlayer (ITL) were studied. To quantify and discriminate between interface-induced and bulk carrier recombination, we employed a one-dimensional diffusion and recombination model. The interface-induced carrier recombination velocity was found to be 1229 ± 78 cm s-1 in nonpassivated MAPbI3 films, which was increased to 2248 ± 75 cm s-1 when MAPbI3 interfaced directly with C60, whereas it was reduced to 145 ± 63 cm s-1 when inserting a 1 nm thin LiF interlayer between MAPbI3 and C60, in turn improving the open-circuit voltage of devices by 33 mV. Second, the effect of surface and grain boundary passivation by PhenHCl in CsFAMA was revealed. Here, the recombination velocity decreased from 605 ± 52 to 0.16 ± 5.28 and 7.294 ± 34.5 cm s-1, respectively. The approach and data analysis presented here are immediately applicable to other perovskite/interlayer/CTL interfaces and passivation protocols, and they add to our understanding of the impact of surfaces and interfaces in MHP-based thin films on carrier recombination and device efficiency.
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The performance of perovskite solar cells with inverted polarity (p-i-n) is still limited by recombination at their electron extraction interface, which also lowers the power conversion efficiency (PCE) of p-i-n perovskite-silicon tandem solar cells. A MgFx interlayer with thickness of ~1 nanometer at the perovskite/C60 interface favorably adjusts the surface energy of the perovskite layer through thermal evaporation, which facilitates efficient electron extraction and displaces C60 from the perovskite surface to mitigate nonradiative recombination. These effects enable a champion open-circuit voltage of 1.92 volts, an improved fill factor of 80.7%, and an independently certified stabilized PCE of 29.3% for a monolithic perovskite-silicon tandem solar cell ~1 square centimeter in area. The tandem retained ~95% of its initial performance after damp-heat testing (85°C at 85% relative humidity) for >1000 hours.
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BACKGROUND: One of the key forces shaping proteins is coevolution of amino acid residues. Knowing which residues coevolve in a particular protein may facilitate our understanding of protein evolution, structure and function, and help to identify substitutions that may lead to desired changes in enzyme kinetics. Rubisco, the most abundant enzyme in biosphere, plays an essential role in the process of carbon fixation through photosynthesis, thus facilitating life on Earth. This makes Rubisco an important model system for studying the dynamics of protein fitness optimization on the evolutionary landscape. In this study we investigated the selective and coevolutionary forces acting on large subunit of land plants Rubisco using Markov models of codon substitution and clustering approaches applied to amino acid substitution histories. RESULTS: We found that both selection and coevolution shape Rubisco, and that positively selected and coevolving residues have their specifically favored amino acid composition and pairing preference. The mapping of these residues on the known Rubisco tertiary structures showed that the coevolving residues tend to be in closer proximity with each other compared to the background, while positively selected residues tend to be further away from each other. This study also reveals that the residues under positive selection or coevolutionary force are located within functionally important regions and that some residues are targets of both positive selection and coevolution at the same time. CONCLUSION: Our results demonstrate that coevolution of residues is common in Rubisco of land plants and that there is an overlap between coevolving and positively selected residues. Knowledge of which Rubisco residues are coevolving and positively selected could be used for further work on structural modeling and identification of substitutions that may be changed in order to improve efficiency of this important enzyme in crops.
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Secuencias de Aminoácidos/genética , Sustitución de Aminoácidos/genética , Evolución Molecular , Filogenia , Plantas/genética , Ribulosa-Bifosfato Carboxilasa/genética , Selección Genética , Análisis por Conglomerados , Codón/genética , Biología Computacional , Funciones de Verosimilitud , Modelos GenéticosRESUMEN
Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of the genetic information-processing systems. In this study, we report the design and construction of a genetic sequential logic circuit in Escherichia coli. It can generate different outputs in response to the same input signal on the basis of its internal state, and 'memorize' the output. The circuit is composed of two parts: (1) a bistable switch memory module and (2) a double-repressed promoter NOR gate module. The two modules were individually rationally designed, and they were coupled together by fine-tuning the interconnecting parts through directed evolution. After fine-tuning, the circuit could be repeatedly, alternatively triggered by the same input signal; it functions as a push-on push-off switch.
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Redes Reguladoras de Genes , Modelos Genéticos , Sitios de Unión , Simulación por Computador , Escherichia coli/genética , Escherichia coli/efectos de la radiación , Mutación/genética , Ribosomas/metabolismo , Transducción de Señal/efectos de la radiación , Rayos UltravioletaRESUMEN
The efficiency of state-of-the-art perovskite solar cells is limited by carrier recombination at defects and interfaces. Thus, understanding these losses and how to reduce them is the way forward toward the Shockley-Queisser limit. Here, we demonstrate that ultrafast transient absorption spectroscopy can directly probe hole extraction and recombination dynamics at perovskite/hole transport layer (HTL) interfaces. To illustrate this, we employed PDPP-3T as HTL because its ground-state absorption is at lower energy than the perovskite's photobleach, enabling direct monitoring of interfacial hole extraction and recombination. Moreover, by fitting the carrier dynamics using a diffusion model, we determined the carrier mobility. Afterwards, by varying the perovskite thickness, we distinguished between carrier diffusion and carrier extraction at the interface. Lastly, we prepared device-like structures, TiO2/perovskite/PDPP-3T stacks, and observed reduced carrier recombination in the perovskite. From PDPP-3T carrier dynamics, we deduced that hole extraction is one order faster than recombination of holes at the interface.
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PURPOSE: To determine the immunogenic characterization of amniotic epithelium (AE), by examining the fate of allogeneic AE grafts heterotopically transplanted in the eye. METHODS: Intact AE from enhanced green fluorescence protein (EGFP) transgenic mice (C57BL/6 background) and wild-type C57BL/6 mice were transplanted onto cornea or conjunctiva, or inserted into the anterior chamber (AC) of normal BALB/c mice, C57BL/6 mice, or BALB/c mice presensitized to donor antigens. For repeated AE transplantation experiments, AE was grafted in the other eye 7 days after the first grafting. Graft fate was assessed clinically and histologically at selected intervals after grafting. Infiltrating inflammatory cells were examined immunohistochemically. Sensitization to alloantigens by AE was assessed by the delayed hypersensitivity (DH) response. RESULTS: In normal recipients, GFP+ cells were absent in EGFP donor-derived AE grafts by day 21 on cornea and by day 7 on conjunctiva. AE grafts implanted in the AC survived for >8 weeks. In presensitized recipients and recipients that underwent repeated AE implantation, graft survival was markedly shorter than in normal recipients. DH was induced at 2 weeks, but failed to be induced at 4 weeks after grafting on cornea or at 8 weeks after grafting on conjunctiva and in the AC of normal recipients. CONCLUSIONS: Fresh allogeneic AE expressed immunogenicity when placed on the ocular surface, although no memory of allospecific DH was acquired. Allogeneic AE is clearly vulnerable to immune rejection in specifically sensitized recipients.
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Amnios/inmunología , Amnios/trasplante , Cámara Anterior/cirugía , Conjuntiva/cirugía , Córnea/cirugía , Animales , Cámara Anterior/inmunología , Trasplante de Células , Conjuntiva/inmunología , Córnea/inmunología , Epitelio/inmunología , Epitelio/trasplante , Femenino , Supervivencia de Injerto/inmunología , Proteínas Fluorescentes Verdes/metabolismo , Hipersensibilidad Tardía/inmunología , Isoantígenos/inmunología , Sustancias Luminiscentes/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Fluorescente , Embarazo , Trasplante HomólogoRESUMEN
We review recent experimental evidence of the immunosuppressive and immunogenic potential of amniotic epithelial cells. Since cryopreserved amniotic membrane (AM) has been used in clinical applications, much research has focused on the beneficial effects of amniotic stromal matrix rather than on the function of viable amniotic cells. However, viable human amniotic epithelial cells (HAECs) have been shown to elicit beneficial effects on secretion of anti-inflammatory factors. Topical application of culture supernatant from HAECs leads to profound suppression of suture-induced neovascularization in cornea and fewer major histocompatibility complex (MHC) class II antigen-presenting cells (APCs) in inflamed cornea after thermal cautery. Furthermore, expression of interleukin (IL)-1beta mRNA was suppressed in cauterized cornea. These results suggest that HAECs are a source of soluble anti-inflammatory factors that suppress corneal inflammation. However, viable amniotic epithelial cells display antigenicity and immunogenicity as allografts. Fresh allogeneic amniotic epithelium (AE) expresses MHC class I antigens and sensitizes recipients when placed in the eye, although long-term memory of allo-specific delayed hypersensitivity (DH) was not acquired. Allogeneic AE was clearly vulnerable to acute immune rejection in specifically sensitized recipients and recipients of repeated AE transplantation. We therefore suggest that immunogenicity of AE should not be ignored, and use of AM from different donor placentas should be emphasized when repeated AM transplantation is required in patients clinically.
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Amnios/inmunología , Amnios/trasplante , Inhibidores de la Angiogénesis/inmunología , Inhibidores de la Angiogénesis/uso terapéutico , Antiinflamatorios/inmunología , Antiinflamatorios/uso terapéutico , Apósitos Biológicos , Enfermedades de la Córnea/inmunología , Enfermedades de la Córnea/cirugía , Neovascularización de la Córnea/prevención & control , Epitelio/inmunología , Humanos , Cicatrización de Heridas/inmunologíaRESUMEN
The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.
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Linfocitos T CD8-positivos/inmunología , Trasplante de Córnea , Galectinas/metabolismo , Supervivencia de Injerto/inmunología , Inmunidad/inmunología , Animales , Cámara Anterior/inmunología , Cámara Anterior/patología , Muerte Celular , Citoprotección , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Corneal/patología , Galectinas/antagonistas & inhibidores , Galectinas/genética , Rechazo de Injerto/inmunología , Receptor 2 Celular del Virus de la Hepatitis A , Tejido Linfoide/metabolismo , Masculino , Ratones , Receptores Virales/antagonistas & inhibidores , Receptores Virales/genética , Receptores Virales/metabolismo , Trasplante HomólogoRESUMEN
PURPOSE: The pathway between the glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) and GITR ligand (GITRL) has been shown to control the function of regulatory T cells (Treg). The present study was conducted to investigate the role of this pathway and Treg in establishing immune privilege status for corneal allografts. METHODS: Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of BALB/c mice, and graft survival was assessed. A separate set of BALB/c mice received an anterior chamber injection of C57BL/6 splenocytes, and induction of allo-specific anterior chamber-associated immune deviation was assessed. Recipients were intraperitoneally administrated anti-GITRL, anti-CD25 monoclonal antibodies (mAb), or control immunoglobulin (IgG). Expressions of GITRL, GITR, and Foxp3 in the allografts were assessed. In vitro, cornea pretreated with anti-GITRL mAb or control IgG was incubated with T cells, and destruction of corneal endothelial cells and the population of Foxp3(+)CD25(+)CD4(+) T cells were assessed. RESULTS: GITRL was expressed constitutively in the cornea and iris-ciliary body. GITRL-expressing allografts were infiltrated with Foxp3+GITR+CD25+CD4(+) T cells. Blockade of GITRL did not affect allo-specific ACAID but led to infiltration of Foxp3(-)CD4(+) T cells and allograft rejection. Depletion of CD25+CD4(+) Treg also accelerated allograft rejection. Destruction of corneal endothelial cells by T cells was significantly enhanced in GITRL-blocked cornea compared with control cornea. Foxp3+CD25+CD4(+) T cells were increased after incubation with GITRL-expressing cornea, but not with GITRL-blocked cornea. CONCLUSIONS: Presence of Foxp3+CD25+CD4(+) Treg in the allograft is necessary for allograft survival. GITRL-dependent expansion of Treg within the cornea is one mechanism underlying immune privilege in corneal allografts.
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Córnea/inmunología , Trasplante de Córnea , Supervivencia de Injerto/inmunología , Receptores de Factor de Crecimiento Nervioso/fisiología , Receptores del Factor de Necrosis Tumoral/fisiología , Linfocitos T Reguladores/inmunología , Factores de Necrosis Tumoral/fisiología , Animales , Cámara Anterior/inmunología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Indirecta , Factores de Transcripción Forkhead/inmunología , Proteína Relacionada con TNFR Inducida por Glucocorticoide , Subunidad alfa del Receptor de Interleucina-2/inmunología , Ligandos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Bazo , Trasplante HomólogoRESUMEN
The present study determined whether topical latanoprost, a prostaglandin (PG) F(2alpha) analog, influences the induction of anterior chamber-associated immune deviation (ACAID), corneal neovascularization (NV) or survival of corneal allografts in mice. BALB/c mice received topical latanoprost or PGE(2) once or multiple times daily starting 4 weeks prior to or the day of anterior chamber injection of C57BL/6 splenocytes. Induction of allo-specific ACAID was assessed by ear challenge with C57BL/6 splenocytes 1 week after subcutaneous immunization. In a separate experiment, orthotopic corneal transplantation was performed using C57BL/6 mice as donors and BALB/c mice as recipients. Recipients were randomized in a masked fashion to receive topical latanoprost or PGE(2). Graft fate was assessed clinically under surgical microscopy. Presence of MHC class II(+) CD11c(+) or CD11b(+) cells in normal BALB/c mouse eyes following latanoprost or PGE(2) administration was assessed immunohistochemically. Control mice received topical 20% dimethyl sulfoxide or no treatment. Allo-specific ACAID was induced after 2 or 6 weeks of once daily treatment with latanoprost, and was induced even after 6 weeks of multiple treatments with latanoprost. Conversely, mice receiving PGE(2) failed to develop ACAID. Opacity and corneal NV scores for allografts treated with latanoprost were statistically indistinguishable from those for control allografts (p>0.05), whereas all allografts treated with PGE(2) were rejected. Opacity and NV scores were significantly higher in these allografts than in controls (p<0.05). A number of MHC class II(+) CD11c(+) cells were present in the central cornea after PGE(2) treatment. Topical application of latanoprost does not influence induction of ACAID or graft outcomes including opacity and NV, whereas PGE(2) does. Immune privilege of corneal allograft is maintained after topical latanoprost application in mice.
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Antihipertensivos/farmacología , Trasplante de Córnea/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Prostaglandinas F Sintéticas/farmacología , Animales , Cámara Anterior/inmunología , Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Córnea/anatomía & histología , Córnea/efectos de los fármacos , Córnea/inmunología , Dinoprostona/farmacología , Antígenos de Histocompatibilidad Clase II/análisis , Latanoprost , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
The programmed death-1 (PD-1) costimulatory pathway has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in establishing an immune privilege status of corneal allografts in mice. B7-H1, but not B7-DC or PD-1, was expressed constitutively in the eye, i.e., cornea, iris-ciliary body, and retina. After corneal allografting, PD-1(+)CD4(+) T cells infiltrated and adhered with B7-H1(+) corneal endothelium. Blockade of PD-1 or B7-H1, but not B7-DC, led to accelerated corneal allograft rejection. In B7-H1-expressing corneal allografts, apoptosis of the infiltrating PD-1(+)CD4(+) or CD8(+) T cells was observed, after which there was allograft acceptance. In contrast, B7-H1 blockade suppressed apoptosis of infiltrating PD-1(+) T cells, which led to allograft rejection. In vitro, destruction of corneal endothelial cells by alloreactive T cells was enhanced when the cornea was pretreated with anti-B7-H1 Ab. This is the first demonstration that the constitutive expression of B7-H1 plays a critical role in corneal allograft survival. B7-H1 expressed on corneal endothelial cells maintains long-term acceptance of the corneal allografts by inducing apoptosis of effector T cells within the cornea.
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Apoptosis , Antígeno B7-1/metabolismo , Córnea/inmunología , Trasplante de Córnea/inmunología , Rechazo de Injerto/inmunología , Glicoproteínas de Membrana/metabolismo , Péptidos/metabolismo , Animales , Anticuerpos Monoclonales/farmacología , Antígenos de Superficie/genética , Antígenos de Superficie/metabolismo , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Antígeno B7-1/análisis , Antígeno B7-H1 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Córnea/metabolismo , Córnea/patología , Células Endoteliales/metabolismo , Rechazo de Injerto/genética , Rechazo de Injerto/patología , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/genética , Masculino , Glicoproteínas de Membrana/antagonistas & inhibidores , Ratones , Ratones Endogámicos , Péptidos/antagonistas & inhibidores , Proteína 2 Ligando de Muerte Celular Programada 1 , Receptor de Muerte Celular Programada 1 , Trasplante HomólogoRESUMEN
Human amniotic epithelial cells (HAEC) may be a source of soluble anti-inflammatory factors. The purpose of this study is to determine the effect of topically applied HAEC culture supernatant on corneal inflammatory reactions. HAEC were obtained from a placenta and cultured for 48 hr, and the supernatant was collected. The conditioned medium from HAEC contained small amounts of human interleukin-1 receptor antagonist (IL-1ra). Intrastromal sutures were placed in the cornea of BALB/c mice to induce corneal neovascularisation. Superficial cauterisation was applied to induce recruitment or activation of antigen presenting cells (APCs) in the cornea without neovascularisation. HAEC conditioned medium, placebo, or recombinant human IL-1ra was topically applied three times daily for 2 weeks. Suture-induced corneal neovascularisation was evaluated microscopically for 8 weeks. The cauterised corneas were harvested at 2 weeks, and the MHC class II(+) APCs were quantified by immunofluorescent staining and confocal microscopy. Inflammatory cytokine gene expression in the cauterised corneas was analyzed by a multiprobe ribonuclease protection assay. Conditioned medium from HAEC led to a profound suppression of corneal neovascularisation and fewer MHC class II(+) APCs in the epithelium. In contrast, human IL-1ra was only slightly effective in suppressing corneal inflammatory reactions. mRNA expression of murine IL-1ra and IL-1beta in the cauterised corneas was markedly suppressed after application of the conditioned medium. These results suggest that HAEC are a source of soluble anti-inflammatory factors and that conditioned medium from HAEC contains factors other than IL-1ra that suppress corneal inflammation.