RESUMEN
Plastic waste accumulation and its degradation into microplastics (MPs) and nanoplastics (NPs) pose environmental concerns. Previous studies have indicated that polystyrene (PS)-MPs harm living animals. Extracellular vesicles (EVs) are associated with metabolic reprogramming and mitochondrial dysfunction in various kidney diseases. In this article, we evaluated how PS-MPs affected tubular cells and fibroblasts. The results demonstrated that PS-MPs increased EV production in human tubular cells and caused endoplasmic reticulum (ER) stress-related proteins without inducing inflammation-related proteins in human tubular cells. The uptake of PS-MPs and incubation with the conditioned medium of PS-MPs induced reactive oxygen species (ROS) production and ER stress-related proteins in fibroblast cells. The fibroblast cells treated with the conditioned medium of PS-MPs also increased the expression of fibrosis-related proteins. Our findings suggested that the expression of EV-related markers increased in tubular cells via Beclin 1 after PS-MP treatment. In addition, PS-MPs induced ROS production in vitro and in vivo. We found that PS-MPs also altered the expression of EV markers in urine, and CD63 expression was also increased in vitro and in vivo after PS-MP treatment. In conclusion, PS-MP-induced EVs lead to ER stress-related proteins, ROS production and fibrosis-related proteins in tubular cells and fibroblasts.
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Vesículas Extracelulares , Microplásticos , Animales , Humanos , Microplásticos/toxicidad , Plásticos , Poliestirenos/toxicidad , Medios de Cultivo Condicionados , Especies Reactivas de Oxígeno , Riñón , Fibroblastos , FibrosisRESUMEN
With rapid industrialization, humans produce an increasing number of products. The composition of these products is usually decomposed. However, some substances are not easily broken down and gradually become environmental pollutants. In addition, these substances may cause bioaccumulation, since the substances can be fragmented into micro- and nanoparticles. These particles or their interactions with other toxic matter circulate in humans via the food chain or air. Whether these micro- and nanoparticles interfere with extracellular vesicles (EVs) due to their similar sizes is unclear. Micro- and nanoparticles (MSs and NSs) induce several cell responses and are engulfed by cells depending on their size, for example, particulate matter with a diameter ≤2.5 µm (PM2.5). Autophagy is a mechanism by which pathogens are destroyed in cells. Some artificial materials are not easily decomposed in organisms. How do these cells or tissues respond? In addition, autophagy operates through two pathways (increasing cell death or cell survival) in tumorigenesis. Many MSs and NSs have been found that induce autophagy in various cells and tissues. As a result, this review focuses on how these particles interfere with cells and tissues. Here, we review MSs, NSs, and PM2.5, which result in different autophagy-related responses in various tissues or cells.
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Autofagia , Contaminantes Ambientales/efectos adversos , Nanopartículas/efectos adversos , Material Particulado/efectos adversos , Animales , Contaminantes Ambientales/toxicidad , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patología , Humanos , Nanopartículas/toxicidad , Neoplasias/etiología , Neoplasias/metabolismo , Neoplasias/patología , Tamaño de la Partícula , Material Particulado/toxicidadRESUMEN
Plastic products are inexpensive, convenient, and are have many applications in daily life. We overuse plastic-related products and ineffectively recycle plastic that is difficult to degrade. Plastic debris can be fragmented into smaller pieces by many physical and chemical processes. Plastic debris that is fragmented into microplastics or nanoplastics has unclear effects on organismal systems. Recently, this debris was shown to affect biota and to be gradually spreading through the food chain. In addition, studies have indicated that workers in plastic-related industries develop many kinds of cancer because of chronic exposure to high levels of airborne microplastics. Microplastics and nanoplastics are everywhere now, contaminating our water, air, and food chain. In this review, we introduce a classification of plastic polymers, define microplastics and nanoplastics, identify plastics that contaminate food, describe the damage and diseases caused by microplastics and nanoplastics, and the molecular and cellular mechanisms of this damage and disease as well as solutions for their amelioration. Thus, we expect to contribute to the understanding of the effects of microplastics and nanoplastics on cellular and molecular mechanisms and the ways that the uptake of microplastics and nanoplastics are potentially dangerous to our biota. After understanding the issues, we can focus on how to handle the problems caused by plastic overuse.
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Nanoestructuras/química , Plásticos/química , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Genotipo , Humanos , Mutación/genética , Transducción de Señal/efectos de los fármacos , Cloruro de Sodio/farmacologíaRESUMEN
Although a vesicular nucleocytoplasmic transport system is believed to exist in eukaryotic cells, the features of this pathway are mostly unknown. Here, we report that the BFRF1 protein of the Epstein-Barr virus improves vesicular transport of nuclear envelope (NE) to facilitate the translocation and clearance of nuclear components. BFRF1 expression induces vesicles that selectively transport nuclear components to the cytoplasm. With the use of aggregation-prone proteins as tools, we found that aggregated nuclear proteins are dispersed when these BFRF1-induced vesicles are formed. BFRF1-containing vesicles engulf the NE-associated aggregates, exit through from the NE, and putatively fuse with autophagic vacuoles. Chemical treatment and genetic ablation of autophagy-related factors indicate that autophagosome formation and autophagy-linked FYVE protein-mediated autophagic proteolysis are involved in this selective clearance of nuclear proteins. Remarkably, vesicular transport, elicited by BFRF1, also attenuated nuclear aggregates accumulated in neuroblastoma cells. Accordingly, induction of NE-derived vesicles by BFRF1 facilitates nuclear protein translocation and clearance, suggesting that autophagy-coupled transport of nucleus-derived vesicles can be elicited for nuclear component catabolism in mammalian cells.-Liu, G.-T., Kung, H.-N., Chen, C.-K., Huang, C., Wang, Y.-L., Yu, C.-P., Lee, C.-P. Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy.
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Autofagia , Proteínas de la Membrana/metabolismo , Membrana Nuclear/metabolismo , Proteínas Virales/metabolismo , Transporte Activo de Núcleo Celular , Autofagosomas/metabolismo , Células HeLa , Humanos , Proteínas de la Membrana/genética , Proteínas Virales/genéticaRESUMEN
The accumulation of fat, which results in obesity, is related to many metabolic disorders. Besides white and brown adipose tissue, beige adipose tissue has recently been recognized as a new type of accumulated fat. Mesenchymal stem cells (MSCs) have been shown to differentiate into brown adipocytes. Through analyzing levels of mRNA and protein markers associated with beige adipocyte, we found concomitant beige adipocyte differentiation upon induction of MSCs into brown adipocytes in a defined medium containing triiodothyronine, insulin, dexamethasone, and indomethacin. Moreover, we found that protein kinase A (PKA) modulators regulated MSC differentiation into brown or beige adipocytes. Activation of PKA by isobutylmethylxanthine or forskolin increased brown adipocyte differentiation and reduced beige adipocyte differentiation, while inactivation of PKA by KT-5720 or SC-3010 or the knockdown of PKA downstream cAMP response element-binding protein (CREB) decreased brown adipocyte differentiation and increased beige adipocyte differentiation. We also showed that increased brown adipocyte differentiation was accompanied by an increase in mitochondrial mass. In conclusion, we propose a model of beige/brown co-differentiation in MSCs and develop a method for controlling this differentiation via PKA modulation.
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Adipocitos Beige/efectos de los fármacos , Adipocitos Marrones/efectos de los fármacos , Medios de Cultivo/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Células Madre Mesenquimatosas/efectos de los fármacos , 1-Metil-3-Isobutilxantina/farmacología , Adipocitos Beige/citología , Adipocitos Beige/metabolismo , Adipocitos Marrones/citología , Adipocitos Marrones/metabolismo , Carbazoles/farmacología , Diferenciación Celular/efectos de los fármacos , Colforsina/farmacología , Medios de Cultivo/química , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/antagonistas & inhibidores , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Dexametasona/farmacología , Regulación de la Expresión Génica , Humanos , Indometacina/farmacología , Insulina/farmacología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Cultivo Primario de Células , Pirroles/farmacología , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Triyodotironina/farmacologíaRESUMEN
The objective of this study was to investigate the effects of combined low-pressure ultraviolet (LPUV) irradiation and free chlorination on the formation of trichloronitromethane (TCNM) byproduct from amine precursors, including a commonly used polyamine coagulant aid (poly(epichlorohydrin dimethylamine)) and simple alkylamines dimethylamine (DMA) and methylamine (MA). Results showed that TCNM formation can increase up to 15 fold by combined UV/chlorine under disinfection to advanced oxidation conditions. The enhancement effect is influenced by UV irradiance, chlorine dose, and water pH. Extended reaction time leads to the decay of TCNM by direct photolysis. The combined UV/chlorine conditions significantly promoted degradation of polyamine to generate intermediates, including DMA and MA, which are better TCNM precursors than polyamine, and also facilitated transformation of these amine precursors to TCNM. Under combined UV/chlorine, polyamine degradation was likely promoted by radical oxidation, photodecay of chlorinated polyamine, and chlorine oxidation/substitution. Promoted TCNM formation from primary amine MA was primarily due to radicals' involvement. Promoted TCNM formation from secondary amine DMA likely involved a combination of radical oxidation, photoenhanced chlorination reactions, and other unknown mechanisms. Insights obtained in this study are useful for reducing TCNM formation during water treatment when both UV and chlorine will be encountered.
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Aminas/química , Cloro/química , Desinfección/métodos , Hidrocarburos Clorados/química , Rayos Ultravioleta , Cloro/administración & dosificación , Dimetilaminas/química , Halogenación , Hidrocarburos Clorados/efectos de la radiación , Iones , Fotólisis , Poliaminas/química , Agua/química , Purificación del Agua/métodosRESUMEN
Metal nanoparticles (M-NPs) have garnered significant attention due to their unique properties, driving diverse applications across packaging, biomedicine, electronics, and environmental remediation. However, the potential health risks associated with M-NPs must not be disregarded. M-NPs' ability to accumulate in organs and traverse the blood-brain barrier poses potential health threats to animals, humans, and the environment. The interaction between M-NPs and various cellular components, including DNA, multiple proteins, and mitochondria, triggers the production of reactive oxygen species (ROS), influencing several cellular activities. These interactions have been linked to various effects, such as protein alterations, the buildup of M-NPs in the Golgi apparatus, heightened lysosomal hydrolases, mitochondrial dysfunction, apoptosis, cell membrane impairment, cytoplasmic disruption, and fluctuations in ATP levels. Despite the evident advantages M-NPs offer in diverse applications, gaps in understanding their biocompatibility and toxicity necessitate further research. This review provides an updated assessment of M-NPs' pros and cons across different applications, emphasizing associated hazards and potential toxicity. To ensure the responsible and safe use of M-NPs, comprehensive research is conducted to fully grasp the potential impact of these nanoparticles on both human health and the environment. By delving into their intricate interactions with biological systems, we can navigate the delicate balance between harnessing the benefits of M-NPs and minimizing potential risks. Further exploration will pave the way for informed decision-making, leading to the conscientious development of these nanomaterials and safeguarding the well-being of society and the environment.
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Nanopartículas del Metal , Nanopartículas , Animales , Humanos , Estrés Oxidativo , Nanopartículas del Metal/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Mitocondrias/metabolismoRESUMEN
Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.
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Nanopartículas , Nanoestructuras , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Nanopartículas/uso terapéutico , Inmunoterapia , Autofagia , Microambiente TumoralRESUMEN
Cigarette smoke (CS) is a risk factor for chronic obstructive pulmonary disease. We attempted to investigate fully the possible effects of CS on kidney cells. We found that the viability of a human kidney proximal tubular epithelial cell line (HK-2 cells) was decreased after treatment with CS extract (CSE). In particular, the effects of CSE at low concentrations did not change the expression of apoptosis and necrosis. Furthermore, CSE increased autophagy- and fibrosis-related proteins in HK-2 cells. Senescence-related proteins and the senescence-associated secretory phenotype (SASP) increased after HK-2 cells were treated with CSE. In addition, both RNA sequencing and gene set enrichment analysis data revealed that glucose-6-phosphate dehydrogenase (G6PD) in the reactive oxygen species (ROS) pathway is responsible for the changes in CSE-treated HK-2 cells. CSE increased G6PD expression and its activity. Moreover, the inhibition of G6PD activity increased senescence in HK-2 cells. The inhibition of autophagy reinforced senescence in the CSE-treated cells. In a mouse model of CS exposure, CS caused kidney damage, including tubular injury and glomerulosclerosis. CS increased fibrosis, autophagy, and G6PD expression in kidney tissue sections. In conclusion, CS induced G6PD expression, autophagy, fibrosis, and senescence in kidney cells. G6PD has a protective role in CS-induced nephrotoxicity.
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Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Animales , Autofagia , Fumar Cigarrillos/efectos adversos , Células Epiteliales/metabolismo , Fibrosis , Glucosafosfato Deshidrogenasa/metabolismo , Riñón/metabolismo , Ratones , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , NicotianaRESUMEN
Treatments for osteoarthritis would benefit from the enhanced visualization of injured articular cartilage and from the targeted delivery of disease-modifying drugs to it. Here, by using ex vivo human osteoarthritic cartilage and live rats and minipigs with induced osteoarthritis, we report the application of collagen-binding peptides, identified via phage display, that are home to osteoarthritic cartilage and that can be detected via magnetic resonance imaging when conjugated with a superparamagnetic iron oxide. Compared with the use of peptides with a scrambled sequence, hyaluronic acid conjugated with the collagen-binding peptides displayed enhanced retention in osteoarthritic cartilage and better lubricated human osteoarthritic tissue ex vivo. Mesenchymal stromal cells encapsulated in the modified hyaluronic acid and injected intra-articularly in rats showed enhanced homing to osteoarthritic tissue and improved its regeneration. Molecular docking revealed WXPXW as the consensus motif that binds to the α1 chain of collagen type XII. Peptides that specifically bind to osteoarthritic tissue may aid the diagnosis and treatment of osteoarthritic joints.
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Cartílago Articular , Osteoartritis , Animales , Humanos , Ratas , Porcinos , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/metabolismo , Ácido Hialurónico/metabolismo , Lubrificación , Colágeno Tipo XII/metabolismo , Simulación del Acoplamiento Molecular , Porcinos Enanos , Osteoartritis/metabolismo , Regeneración , Péptidos/metabolismoRESUMEN
Microplastics (MPs) pollution has become a serious environmental issue worldwide, but its potential effects on health remain unknown. The administration of polystyrene MPs (PS-MPs) to mice for eight weeks impaired learning and memory behavior. PS-MPs were detected in the brain especially in the hippocampus of these mice. Concurrently, the hippocampus had decreased levels of immediate-early genes, aberrantly enhanced synaptic glutamate AMPA receptors, and elevated neuroinflammation, all of which are critical for synaptic plasticity and memory. Interestingly, ablation of the vagus nerve, a modulator of the gut-brain axis, improved the memory function of PS-MPs mice. These results indicate that exposure to PS-MPs in mice alters the expression of neuronal activity-dependent genes and synaptic proteins, and increases neuroinflammation in the hippocampus, subsequently causing behavioral changes through the vagus nerve-dependent pathway. Our findings shed light on the adverse impacts of PS-MPs on the brain and hippocampal learning and memory.
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Microplásticos , Poliestirenos , Animales , Ácido Glutámico , Hipocampo , Ratones , Plásticos , Poliestirenos/toxicidadRESUMEN
BACKGROUND: Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Previous studies have indicated that particles of these products have several effects on the gut and liver. Polystyrene (PS)-MPs (PS-MPs) induce several responses, such as oxidative stress, and affect living organisms. OBJECTIVES: The aim of this study was to investigate the effects of PS-MPs in kidney cells in vitro and in vivo. METHODS: PS-MPs were evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6 mice. Mitochondrial reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, inflammation, and autophagy were analyzed in kidney cells. In vivo, we evaluated biomarkers of kidney function, kidney ultrastructure, muscle mass, and grip strength, and urine protein levels, as well as the accumulation of PS-MPs in the kidney tissue. RESULTS: Uptake of PS-MPs at different concentrations by HK-2 cells resulted in higher levels of mitochondrial ROS and the mitochondrial protein Bad. Cells exposed to PS-MPs had higher ER stress and markers of inflammation. MitoTEMPO, which is a mitochondrial ROS antioxidant, mitigated the higher levels of mitochondrial ROS, Bad, ER stress, and specific autophagy-related proteins seen with PS-MP exposure. Furthermore, cells exposed to PS-MPs had higher protein levels of LC3 and Beclin 1. PS-MPs also had changes in phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT)/mitogen-activated protein kinase (mTOR) signaling pathways. In an in vivo study, PS-MPs accumulated and the treated mice had more histopathological lesions in the kidneys and higher levels of ER stress, inflammatory markers, and autophagy-related proteins in the kidneys after PS-MPs treatment by oral gavage. CONCLUSIONS: The results suggest that PS-MPs caused mitochondrial dysfunction, ER stress, inflammation, and autophagy in kidney cells and accumulated in HK-2 cells and in the kidneys of mice. These results suggest that long-term PS-MPs exposure may be a risk factor for kidney health. https://doi.org/10.1289/EHP7612.
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Riñón , Microplásticos , Poliestirenos , Animales , Células Epiteliales/efectos de los fármacos , Humanos , Riñón/citología , Riñón/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Microplásticos/toxicidad , Poliestirenos/toxicidadRESUMEN
Vinyl chloride (VC) is a noninfective occupational risk factor. It is found in industrial chemicals, volatile organic compounds, cigarette smoke ingredients, etc. It is a kind of toxic gas that causes many diseases. VC exposure causes an increased risk of liver fibrosis and can result in angiosarcoma of the liver. Previous studies have shown that high-doses of VC exposure in mice resulted in acute death with marked tubular necrosis of the renal cortex. In this study, we assessed the nephrotoxicity of VC in vitro and in vivo. As a result, we demonstrated that VC induced fibrosis-associated protein expression, such as connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1) and collagen 1, and autophagy-associated protein expression, such as Beclin 1 and LC3-II, in kidney cells. The beclin1 siRNA experiments found that autophagy inhibited VC-induced fibrosis. Blood urea nitrogen (BUN) and creatinine levels were increased after VC treatment. Furthermore, VC caused glomerulosclerosis and tubular injury in mouse kidney tissues. Kidney tissue sections showed that VC induced fibrosis and autophagy in mouse kidney tissues. In summary, the results of VC-induced fibrosis suggest that autophagy plays an important role in kidney damage. VC may cause nephrotoxicity, and the results illustrate the importance of considering the toxicological hazards of VC in kidney cells.
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Autofagia/efectos de los fármacos , Riñón/patología , Cloruro de Vinilo/toxicidad , Animales , Biomarcadores/metabolismo , Nitrógeno de la Urea Sanguínea , Línea Celular , Supervivencia Celular/efectos de los fármacos , Creatinina , Fibrosis , Humanos , Riñón/efectos de los fármacos , Túbulos Renales/efectos de los fármacos , Túbulos Renales/lesiones , Túbulos Renales/patología , Masculino , Ratones Endogámicos BALB C , Modelos BiológicosRESUMEN
Fluorenyl-9-methoxycarbonyl (Fmoc)-diphenylalanine (Fmoc-FF) and Fmoc-arginine-glycine--aspartate (Fmoc-RGD) peptides self-assemble to form a 3D network of supramolecular hydrogel (Fmoc-FF/Fmoc-RGD), which provides a nanofibrous network that uniquely presents bioactive ligands at the fiber surface for cell attachment. In the present study, mesenchymal stem cells (MSCs) in Fmoc-FF/Fmoc-RGD hydrogel increase in proliferation and survival compared to those in Fmoc-FF/Fmoc-RGE hydrogel. Moreover, MSCs encapsulated in Fmoc-FF/Fmoc-RGD hydrogel and induced in each defined induction medium undergo in vitro osteogenic, adipogenic, and chondrogenic differentiation. For in vivo differentiation, MSCs encapsulated in hydrogel are induced in each defined medium for one week, followed by injection into gelatin sponges and transplantation into immunodeficient mice for four weeks. MSCs in Fmoc-FF/Fmoc-RGD hydrogel increase in differentiation into osteogenic, adipogenic, and chondrogenic differentiation, compared to those in Fmoc-FF/Fmoc-RGE hydrogel. This study concludes that nanofibers formed by the self-assembly of Fmoc-FF and Fmoc-RGD are suitable for the attachment, proliferation, and multi-differentiation of MSCs, and can be applied in musculoskeletal tissue engineering.
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Diferenciación Celular/efectos de los fármacos , Hidrogeles/farmacología , Células Madre Mesenquimatosas/citología , Péptidos/farmacología , Andamios del Tejido/química , Arginina/análogos & derivados , Arginina/química , Adhesión Celular/efectos de los fármacos , Recuento de Células , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fluorenos/química , Humanos , Hidrogeles/síntesis química , Hidrogeles/química , Células Madre Mesenquimatosas/efectos de los fármacos , Péptidos/químicaRESUMEN
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