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The demand for controllable fragrance materials is substantial owing to their potential to impart enduring scents in a variety of applications. However, the practical application of such materials has been limited by challenges in tunable morphogenesis, structural variability, and adaptability to diverse conditions. In our study, we introduce a hybrid living material that integrates a genetically engineered strain of Kluyveromyces marxianus CBS6556 with an adaptive hydrogel. The engineered K. marxianus achieved temperature stability in 2-phenylethanol (2-PE) and 2-phenylethyl acetate (2-PEAc) production by expressing relevant genes in the 2-PE metabolic pathway using the high-temperature preferential promoter SSE1. The enhanced water retention capacity supports the metabolic activities of the encapsulated yeast cells, ensuring their survival and functionality over an extended period. Fragrance-releasing living material (FLM) is designed to controllably emit fragrance 2-PE by adjusting the microbial concentration within the hydrogel matrix. The FLM exhibits versatile adhesion capabilities, effectively binding to a spectrum of surfaces such as wood, textiles, and glass as well as to natural substrates like leaves. This adaptability enhances the material's applicability across various settings. Furthermore, FLM can be crafted into various forms, including microbeads, fibers, and films. This research opens up new horizons for controlled fragrance release of living materials.
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The acoustic tomography (AT) velocity field reconstruction technique has become a research hotspot in recent years due to its noninvasive nature, high accuracy, and real-time measurement advantages. However, most of the existing studies are limited to the reconstruction of the velocity field in a rectangular area, and there are very few studies on a circular area, mainly because the layout of acoustic transducers, selection of acoustic paths, and division of measured regions are more difficult in a circular area than in a rectangular area. Therefore, based on AT and using the reconstruction algorithm of the Markov function and singular value decomposition (MK-SVD), this paper proposes a measured regional division optimization algorithm for velocity field reconstruction in a circular area. First, an acoustic path distribution based on the multipath effect is designed to solve the problem of the limited emission angle of the acoustic transducer. On this basis, this paper proposes an adaptive optimization algorithm for measurement area division based on multiple sub-objectives. The steps are as follows: first, two optimization objectives, the condition number of coefficient matrix and the uniformity of acoustic path distribution, were designed. Then, the weights of each sub-objective are calculated using the coefficient of variation (CV). Finally, the measured regional division is optimized based on particle swarm optimization (PSO). The reconstruction effect of the algorithm and the anti-interference ability are verified through the reconstruction experiments of the model velocity field and the simulated velocity field.
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Background: Traditional Chinese Medicines have been used for thousands of years but without any sound empirical basis. One such preparation is the Qijudihuang pill (QP), a mixture of eight herbs, that has been used in China for the treatment of various conditions including age-related macular degeneration (AMD), the most common cause of blindness in the aged population. In order to explain the mechanism behind the effect of QP, we used an AMD model of high-fat diet (HFD) fed mice to investigate cholesterol homeostasis, oxidative stress, inflammation and gut microbiota. Methods: Mice were randomly divided into three groups, one group was fed with control diet (CD), the other two groups were fed with high-fat-diet (HFD). One HFD group was treated with QP, both CD and the other HFD groups were treated with vehicles. Tissue samples were collected after the treatment. Cholesterol levels in retina, retinal pigment epithelium (RPE), liver and serum were determined using a commercial kit. The expression of enzymes involved in cholesterol metabolism, inflammation and oxidative stress was measured with qRT-PCR. Gut microbiota was analyzed using 16S rRNA sequencing. Results: In the majority of the lipid determinations, analytes were elevated by HFD but this was reversed by QP. Cholesterol metabolism including the enzymes of bile acid (BA) formation was suppressed by HFD but again this was reversed by QP. BAs play a major role in signaling between host and microbiome and this is disrupted by HFD resulting in major changes in the composition of colonic bacterial communities. Associated with these changes are predictions of the metabolic pathway complexity and abundance of individual pathways. These concerned substrate breakdowns, energy production and the biosynthesis of pro-inflammatory factors but were changed back to control characteristics by QP. Conclusion: We propose that the ability of QP to reverse these HFD-induced effects is related to mechanisms acting to lower cholesterol level, oxidative stress and inflammation, and to modulate gut microbiota.
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Microbioma Gastrointestinal , Degeneración Macular , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Medicina Tradicional China , ARN Ribosómico 16S , Inflamación , Colesterol , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/etiologíaRESUMEN
The spatial heterogeneity of landslide influencing factors is the main reason for the poor generalizability of the susceptibility evaluation model. This study aimed to construct a comprehensive explanatory framework for landslide susceptibility evaluation models based on the SHAP (SHapley Additive explanation)-XGBoost (eXtreme Gradient Boosting) algorithm, analyze the regional characteristics and spatial heterogeneity of landslide influencing factors, and discuss the heterogeneity of the generalizability of the models under different landscapes. Firstly, we selected different regions in typical mountainous hilly region and constructed a geospatial database containing 12 landslide influencing factors such as elevation, annual average rainfall, slope, lithology, and NDVI through field surveys, satellite images, and a literature review. Subsequently, the landslide susceptibility evaluation model was constructed based on the XGBoost algorithm and spatial database, and the prediction results of the landslide susceptibility evaluation model were explained based on regional topography, geology, and hydrology using the SHAP algorithm. Finally, the model was generalized and applied to regions with both similar and very different topography, geology, meteorology, and vegetation, to explore the spatial heterogeneity of the generalizability of the model. The following conclusions were drawn: the spatial distribution of landslides is heterogeneous and complex, and the contribution of each influencing factor on the occurrence of landslides has obvious regional characteristics and spatial heterogeneity. The generalizability of the landslide susceptibility evaluation model is spatially heterogeneous and has better generalizability to regions with similar regional characteristics. Further explanation of the XGBoost landslide susceptibility evaluation model using the SHAP method allows quantitative analysis of the differences in how much various factors contribute to disasters due to spatial heterogeneity, from the perspective of global and local evaluation units. In summary, the integrated explanatory framework based on the SHAP-XGBoost model can quantify the contribution of influencing factors on landslide occurrence at both global and local levels, which is conducive to the construction and improvement of the influencing factor system of landslide susceptibility in different regions. It can also provide a reference for predicting potential landslide hazard-prone areas and for Explainable Artificial Intelligence (XAI) research.
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Desastres , Deslizamientos de Tierra , Sistemas de Información Geográfica , Inteligencia Artificial , Bases de Datos FactualesRESUMEN
Infrared and visible image fusion aims to produce an informative fused image for the same scene by integrating the complementary information from two source images. Most deep-learning-based fusion networks utilize small kernel-size convolution to extract features from a local receptive field or design unlearnable fusion strategies to fuse features, which limits the feature representation capabilities and fusion performance of the network. Therefore, a novel end-to-end infrared and visible image fusion framework called DTFusion is proposed to address these problems. A residual PConv-ConvNeXt module (RPCM) and dense connections are introduced into the encoder network to efficiently extract features with larger receptive fields. In addition, a texture-contrast compensation module (TCCM) with gradient residuals and an attention mechanism is designed to compensate for the texture details and contrast of features. The fused features are reconstructed through four convolutional layers to generate a fused image with rich scene information. Experiments on public datasets show that DTFusion outperforms other state-of-the-art fusion methods in both subjective vision and objective metrics.
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PURPOSE: Age-related macular degeneration (AMD) is the commonest cause of permanent vision loss in the elderly. Traditional Chinese medicine (TCM) has long been used to treat AMD, although the underlying functional mechanisms are not understood. This study aims to predict the active ingredients through screening the chemical ingredients of anti-AMD decoction and to elucidate the underlying mechanisms. METHODS: We collected the prescriptions for effective AMD treatment with traditional Chinese medicine and screened several Chinese medicines that were used most frequently in order to compose "anti-AMD decoction." The pharmacologically active ingredients and corresponding targets in this anti-AMD decoction were mined using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the AMD-related targets were identified through the GeneCards database. Network pharmacology was performed to construct the visual network of anti-AMD decoction-AMD protein-protein interaction (PPI). Further, the Autodock software was adopted for molecular docking on the core active ingredients and core targets. The function of core ingredients against oxidative stress and inflammation in retinal pigment epithelial cells was assessed using biochemical assays. RESULTS: We screened out 268 active ingredients in anti-AMD decoction corresponding to 258 ingredient targets, combined with 2160 disease targets in AMD, and obtained 129 drug-disease common targets. The key core proteins were predominantly involved in inflammation. Furthermore, molecular docking showed that four potential active ingredients (Quercetin, luteolin, naringenin and hederagenin) had good affinity with the core proteins, IL-6, TNF, VEGFA and MAPK3. Quercetin, luteolin and naringenin demonstrated capacities against oxidative stress and inflammation in human retinal pigment epithelial cells. CONCLUSIONS: The data suggests that anti-AMD decoction has multiple functional components and targets in treating AMD, possibly mediated by suppression of oxidative stress and inflammation.
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Medicamentos Herbarios Chinos , Degeneración Macular , Anciano , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Interleucina-6 , Luteolina , Degeneración Macular/tratamiento farmacológico , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Quercetina , Pigmentos RetinianosRESUMEN
Okadaic acid (OA, C44H68O13) is a neurotoxin and phosphatase inhibitor produced by several dinoflagellate species. OA is widely known to accumulate in black sponges and is associated with seafood poisoning. Humans can be exposed to OA by consuming contaminated shellfish that have accumulated toxins during algal blooms. Evidence from in vitro and in vivo studies demonstrate that OA exposure causes neurotoxicity in addition to diarrheal syndrome. It is unclear whether exposure to OA affects retinal function, a part of the central nervous system. We evaluated the toxicity of OA in human retinal pigment epithelial cells (ARPE-19) and in zebrafish retinas. Cell-based assays determined that OA significantly decreased cell viability in a dose-dependent manner and increased oxidative stress, inflammation and cell death compared to the untreated control group. In the in vivo study, zebrafish embryos at 24 h post fertilization (hpf) were treated with/without OA for four days, endpoint measurements including mortality, malformations, delayed hatching, altered heartbeat and reduced movement were performed. OA exposure increased mortality, decreased hatching, heartbeat rate, and caused morphological abnormalities. OA exposure also markedly decreased the expression of antioxidant genes and a significantly increased inflammation as well as evoking a loss of photoreceptors in zebrafish embryos. The data suggest that consuming OA-contaminated seafood can induce retinal toxicity.
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Estrés Oxidativo , Pez Cebra , Animales , Humanos , Inflamación , Ácido Ocadaico/toxicidad , RetinaRESUMEN
Retinitis pigmentosa (RP) is a group of visual disorders caused by mutations in over 70 genes. RP is characterized by initial degeneration of rod cells and late cone cell death, regardless of genetic abnormality. Rod cells are the main consumers of oxygen in the retina, and after the death of rod cells, the cone cells have to endure high levels of oxygen, which in turn leads to oxidative damage and cone degeneration. Gypenosides (Gyp) are major dammarane-type saponins of Gynostemma pentaphyllum that are known to reduce oxidative stress and inflammation. In this project we assessed the protective effect of Gyp against cone cell death in the rpgrip1 mutant zebrafish, which recapitulate the classical pathological features found in RP patients. Rpgrip1 mutant zebrafish were treated with Gyp (50 µg/g body weight) from two-months post fertilization (mpf) until 6 mpf. Gyp treatment resulted in a significant decrease in cone cell death compared to that of untreated mutant zebrafish. A markedly low level of reactive oxygen species and increased expression of antioxidant genes were detected in Gyp-incubated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Similarly, the activities of catalase and superoxide dismutase and the level of glutathione were significantly increased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Gyp treatment also decreased endoplasmic reticulum stress in rpgrip1 mutant eyes. Expression of proinflammatory cytokines was also significantly decreased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Network pharmacology analysis demonstrated that the promotion of cone cell survival by Gyp is possibly mediated by multiple hub genes and associated signalling pathways. These data suggest treatment with Gyp will benefit RP patients.
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Age-related macular degeneration (AMD) is the most common cause of visual impairment in developed countries. Inflammation serves a critical role in the pathogenesis of AMD. Gardenia jasminoides is found in several regions of China and is traditionally used as an organic yellow dye but has also been widely used as a therapeutic agent in numerous diseases, including inflammation, depression, hepatic and vascular disorders, which may reflect the variability of functional compounds that are present in Gardenia jasminoides extracts (GJE). To investigate the therapeutic potential of GJE for AMD, ARPE-19 cells were treated with lipopolysaccharide (LPS) or LPS plus GJE. GJE significantly decreased LPS-induced expression of proinflammatory cytokines, including IL-1ß, IL-6 and TNF-α. In the in vivo study, GJE inhibited CuSO4-induced migration of primitive macrophages to the lateral line in zebrafish embryos. GJE also attenuated expression of cytokines (IL-1ß, IL-6 and TNF-α), NFKB activating protein (nkap) and TLR4 in ARPE-19 cells. The results of the present study demonstrated the anti-inflammatory potential of GJE in vitro and in vivo, and suggested GJE as a therapeutic candidate for AMD.
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Age-related Macular Degeneration (AMD) is a major cause of sight impairment in the elderly with complex aetiology involving genetics and environment and with limited therapeutic options which have limited efficacy. We have previously shown in a mouse-model of the condition, induced by feeding a high fat diet, that adverse effects of the diet can be reversed by co-administration of the TSPO activator, etifoxine. We extend those observations showing improvements in retinal pigment epithelial (RPE) cells with decreased lipids and enhanced expression of cholesterol metabolism and transport enzymes. Further, etifoxine decreased levels of reactive oxygen species (ROS) in RPE and inflammatory cytokines in RPE and serum. With respect to gut microbiome, we found that organisms abundant in the high fat condition (e.g. in the genus Anaerotruncus and Oscillospira) and implicated in AMD, were much less abundant after etifoxine treatment. The changes in gut flora were associated with the predicted production of metabolites of benefit to the retina including tryptophan and other amino acids and taurine, an essential component of the retina necessary to counteract ROS. These novel observations strengthen earlier conclusions that the mechanisms behind improvements in etifoxine-induced retinal physiology involve an interaction between effects on the host and the gut microbiome.
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Colesterol/metabolismo , Metabolismo de los Lípidos , Degeneración Macular/metabolismo , Estrés Oxidativo/fisiología , Receptores de GABA/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Homeostasis , Ligandos , Degeneración Macular/patología , Ratones , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Epitelio Pigmentado de la Retina/patologíaRESUMEN
This article aims to improve the problem of slow convergence speed, poor global search ability, and unknown time-varying dynamic obstacles in the path planning of ant colony optimization in dynamic environment. An improved ant colony optimization algorithm using time taboo strategy is proposed, namely, time taboo ant colony optimization (TTACO), which uses adaptive initial pheromone distribution, rollback strategy, and pheromone preferential limited update to improve the algorithm's convergence speed and global search ability. For the poor global search ability of the algorithm and the unknown time-varying problem of dynamic obstacles in a dynamic environment, a time taboo strategy is first proposed, based on which a three-step arbitration method is put forward to improve its weakness in global search. For the unknown time-varying dynamic obstacles, an occupancy grid prediction model is proposed based on the time taboo strategy to solve the problem of dynamic obstacle avoidance. In order to improve the algorithm's calculation speed when avoiding obstacles, an ant colony information inheritance mechanism is established. Finally, the algorithm is used to conduct dynamic simulation experiments in a simulated factory environment and is compared with other similar algorithms. The experimental results show that the TTACO can obtain a better path and accelerate the convergence speed of the algorithm in a static environment and can successfully avoid dynamic obstacles in a dynamic environment.
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Age-related macular degeneration (AMD) is the most common cause of visual disorder in aged people and may lead to complete blindness with ageing. The major clinical feature of AMD is the presence of cholesterol enriched deposits underneath the retinal pigment epithelium (RPE) cells. The deposits can induce oxidative stress and inflammation. It has been suggested that abnormal cholesterol homeostasis contributes to the pathogenesis of AMD. However, the functional role of defective cholesterol homeostasis in AMD remains elusive. STARD proteins are a family of proteins that contain a steroidogenic acute regulatory protein-related lipid transfer domain. There are fifteen STARD proteins in mammals and some, such as STARD3, are responsible for cholesterol trafficking. Previously there was no study of STARD proteins in retinal cholesterol metabolism and trafficking. Here we examined expression of the Stard3 gene in mouse retinal and RPE cells at ages of 2 and 20 months. We found that expression of Stard 3 gene transcripts in both mouse RPE and retina was significantly decreased at age of 20 months when compared to that of age 2 months old. We created a stable ARPE-19 cell line overexpressing STARD3 and found this resulted in increased cholesterol efflux, reduced accumulation of intracellular oxidized LDL, increased antioxidant capacity and lower levels of inflammatory cytokines. The data suggested that STARD3 is a potential target for AMD through promoting the removal of intracellular cholesterol and slowing the disease progression.
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Lipoproteínas LDL/farmacología , Proteínas de la Membrana/genética , Estrés Oxidativo/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Animales , Línea Celular , Expresión Génica , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , RatonesRESUMEN
Retinal degeneration, characterised by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxysterols and retinal degeneration. Here, we summarise early and recent work related to retina oxysterol-producing enzymes and the distribution of oxysterols in the retina. We examine the impact of loss of oxysterol-producing enzymes on retinal pathology and explore the molecular mechanisms associated with the toxic or protective roles of individual oxysterols in different types of retinal degeneration. We conclude that increased efforts to better understand the oxysterol-associated pathophysiology will help in the development of effective retinal degeneration therapies. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.
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Oxiesteroles , Degeneración Retiniana , Colesterol , Humanos , Metabolismo de los Lípidos , RetinaRESUMEN
At present, there are two ways to obtain temperature information: contact type and nonintrusive type. As a nonintrusive temperature measurement method, ultrasonic thermometry can be used to acquire the temperature distribution of complex fields conveniently. By measuring the time-of-flight (TOF) between ultrasonic transmitters and receivers, and according to the relationship between temperature and ultrasonic velocity, the temperature distribution can be reconstructed. Among the existing algorithms, the least square method (LSM) will lose much information near the edges of the temperature field, and the algebra reconstruction technique (ART) is time-consuming with low reconstruction accuracy. In this article, an improved reconstruction algorithm based on an inverse quadratic function and singular value decomposition (IQ-SVD) is proposed, which can effectively increase the reconstruction accuracy. The simulations of the real temperature data are conducted in ideal and noisy environments, respectively. Moreover, the influence of region division and shape parameters on reconstruction accuracy is discussed. The simulation results indicate that, compared with conventional algorithms, the proposed algorithm can accurately reflect the temperature distribution, and the root mean square error in the central region and the edge region is reduced by 0.49% at least, and 1.28% at most.
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Retinitis pigmentosa (RP) is a collection of heterogenous genetic retinal disorders resulting in cumulative retinal deterioration involving progressive loss of photoreceptors and eventually in total blindness. Oxidative stress plays a central role in this photoreceptor loss. Gypenosides (Gyp) are the main functional component isolated from the climbing vine Gynostemma pentaphyllum and have been shown to defend cells against the effects of oxidative stress and inflammation, providing protection in experimentally-induced optic neuritis. The zebrafish model has been used to investigate a range of human diseases. Previously we reported early retinal degeneration in a mutant zebrafish line carrying a point-nonsense mutation in the retinitis pigmentosa GTPase regulator interacting protein 1 (rpgrip1) gene that is mutated in RP patients. The current study investigated the potential protective effects of Gyp against photoreceptor degeneration in the Rpgrip1 deleted zebrafish. Rpgrip1 mutant zebrafish were treated with 5 µg/ml of Gyp in E3 medium from 6 h post fertilization (hpf) till 1 month post fertilization (mpf). Rpgrip1 mutant zebrafish treated with 5 µg/ml of Gyp showed a significant decrease by 68.41% (p = 0.0002) in photoreceptor cell death compared to that of untreated mutant zebrafish. Expression of antioxidant genes catalase, sod1, sod2, gpx1, gclm, nqo-1 and nrf-2 was significantly decreased in rpgrip1 mutant zebrafish eyes by 61.51%, 77.40%, 60.11%, 81.17%, 72.07%, 78.95% and 85.42% (all p < 0.0001), respectively, when compared to that of wildtype zebrafish; superoxide dismutase and catalase activities, and glutathione levels in rpgrip1 mutant zebrafish eyes were significantly decreased by 87.21%, 21.55% and 96.51% (all p < 0.0001), respectively. There were marked increases in the production of reactive oxygen species (ROS) and malondialdehyde (MDA) by 2738.73% and 510.69% (all p < 0.0001), respectively, in rpgrip1 mutant zebrafish eyes; expression of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α was also significantly increased by 150.11%, 267.79% and 190.72% (all p < 0.0001), respectively, in rpgrip1 mutant zebrafish eyes, compared to that of wildtype zebrafish. Treatment with Gyp significantly counteracted these effects. This study indicates that Gyp has a potential role in the treatment of RP.
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Estrés Oxidativo , Células Fotorreceptoras de Invertebrados/efectos de los fármacos , Retina/efectos de los fármacos , Retinitis Pigmentosa/tratamiento farmacológico , Animales , Gynostemma , Inmunohistoquímica , Células Fotorreceptoras de Invertebrados/metabolismo , Células Fotorreceptoras de Invertebrados/patología , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Retina/metabolismo , Retina/patología , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/patología , Rodopsina/metabolismo , Pez CebraRESUMEN
Retinal degeneration is characterized by the dysfunction of retinal cells. Oxidative and endoplasmic reticulum (ER) stress play an important role in the pathogenesis and progression of retinal degeneration. Tauroursodeoxycholic acid (TUDCA) has been demonstrated to have protective effects in in vitro and in vivo retinal degeneration models. To fully understand the molecular mechanisms of TUDCA's protection, we first treated human retinal pigment epithelial (RPE) cells, ARPE-19, with H2O2 or H2O2 plus TUDCA for 24 h. RPE cells co-exposed to TUDCA had higher cell viability and lower cell death rate compared to cells exposed to H2O2 alone. TUDCA significantly increased antioxidant capacity in H2O2-treated RPE cells by decreasing the generation of reactive oxygen species (ROS) and Malondialdehyde (MDA), upregulating the expression of antioxidant genes, and increasing the generation of glutathione (GSH). TUDCA also inhibited inflammation in H2O2-challenged RPE cells by decreasing the expression of proinflammatory cytokines. Furthermore, TUDCA suppressed thapsigargin-induced ER stress in RPE cells, as demonstrated by decreased the expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and apoptosis. Our present study suggests that TUDCA can protect RPE cells against oxidative damage, inflammation, and ER stress and may benefit patients with retinal degeneration.
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Diabetic retinopathy (DR) is a diabetes-associated complication characterized by irreversible deterioration of the microvessels within the retina, leading subsequently to severe retinal damage and vision loss. Vitamin D (VITD), a steroid hormone, plays multiple physiological functions in cellular homeostasis. Deficiency of VITD has been suggested to be associated with DR. To study the potential protective function of VITD in DR, high-glucose-treated ARPE-19 cells and STZ-induced diabetic mice were used as in vitro and in vivo models. The protective effects of VITD were assessed based on the changes of expression of antioxidant enzymes and cytokines in high-glucose-treated retinal pigment epithelial (RPE) cells and in the retina and RPE of diabetic and VITD-treated diabetic mice. The present study demonstrated that exposure to a high level of glucose caused upregulation of pro-inflammatory cytokines and a decrease in anti-oxidant enzyme expression in both in vitro and in vivo models. VITD treatment increased cell viability, reduced reactive oxygen species (ROS) production and caspase-3/7 activities in high-glucose-treated RPE cells. Our data suggest that VITD can protect the retina and RPE from high-glucose-induced oxidative damage and inflammation.
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Citoprotección/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Glucosa/efectos adversos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Vitamina D/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/patología , Retinopatía Diabética/patología , Retinopatía Diabética/prevención & control , Relación Dosis-Respuesta a Droga , Células Epiteliales/fisiología , Glucosa/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Epitelio Pigmentado de la Retina/fisiología , Estreptozocina , Vitamina D/uso terapéuticoRESUMEN
Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L, cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton organization. The actin cytoskeleton rearrangement is regulated by the small GTPase RhoA via the planar cell polarity (PCP) pathway. RhoA activity was upregulated in the absence of RPGR, RPGRIP1 or RPGRIP1L proteins. In RPGR, RPGRIP1 or RPGRIP1L KD cells, we observed increased levels of DVl2 and DVl3 proteins, the core components of the PCP pathway, due to impaired proteasomal activity. RPGR, RPGRIP1 or RPGRIP1L KD cells treated with thapsigargin (TG), an inhibitor of sarcoendoplasmic reticulum Ca2+- ATPases, showed impaired store-operated Ca2+ entry (SOCE), which is mediated by STIM1 and Orai1 proteins. STIM1 was not localized to the ER-PM junction upon ER store depletion in RPGR, RPGRIP1 or RPGRIP1L KD cells. Our results demonstrate that the RPGR protein complex is required for regulating proteasomal activity and for modulating SOCE, which may contribute to the ciliopathy phenotype.
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Sodium alginate (SA) beads with ultrahigh adsorption capacity were prepared via hydrogen bonds between SA and 2-acrylamido-2-methylpropa-1-propanesulfonic acid (AMPS), and the AMPS was then post-cross-linked to manufacture SA/PAMPS beads. The equilibrium adsorption capacities of methylene blue (MB) and Pb2+ for the SA/PAMPS10 beads were 2977 and 2042â¯mg/g, respectively. Although the SA beads exhibited higher equilibrium adsorption capacities of MB and Pb2+ than those of the SA/PAMPS10 beads, the SA/PAMPS10 beads had better mechanical property and higher stability. The pseudo-second-order kinetic model and the Langmuir isotherm described the adsorption processes of the SA/PAMPS10 beads for MB well. In addition, the SA/PAMPS10 beads could be reused with stable adsorption capacity for at least three cycles. The beads also had excellent performances on absorbing methylene violet and other heavy metal ions (Cu2+, Cd2+ and Ni2+). Therefore, the SA-based beads with high adsorption capacity might be good candidates for industrial pollutant treatments.
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Alginatos/química , Cationes/química , Colorantes/química , Adsorción , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Cinética , Metales Pesados/química , Contaminantes Químicos del Agua , Purificación del AguaRESUMEN
Oxidative stress plays a critical role in the pathogenesis of retinal degeneration. Gypenosides are the major functional components isolated from Gynostemma pentaphyllum. They have been shown to protect against oxidative stress and inflammation and have also demonstrated a protective effect on experimental optic neuritis. In order to determine the protective properties of gypenosides against oxidative stress in human retinal pigment epithelium (RPE) cells, ARPE-19â¯cells were treated with H2O2 or H2O2 plus gypenosides for 24â¯h. ARPE-19â¯cells co-treated with gypenosides had significantly increased cell viability and decreased cell death rate when compared to cells treated with H2O2 alone. The level of GSH, the activities of SOD and catalase, and the expression of NRF2 and antioxidant genes were notably decreased, while there were marked increases in ROS, MDA and pro-inflammatory cytokines in ARPE-19â¯cells exposed to H2O2; co-treatment with gypenosides significantly counteract these changes. Our study suggests that gypenosides protect RPE cells from oxidative damage and offer therapeutic potential for the treatment of retinal degeneration.