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The two-dimensional sample entropy marks a significant advance in evaluating the regularity and predictability of images in the information domain. Unlike the direct computation of sample entropy, which incurs a time complexity of O(N2) for the series with N length, the Monte Carlo-based algorithm for computing one-dimensional sample entropy (MCSampEn) markedly reduces computational costs by minimizing the dependence on N. This paper extends MCSampEn to two dimensions, referred to as MCSampEn2D. This new approach substantially accelerates the estimation of two-dimensional sample entropy, outperforming the direct method by more than a thousand fold. Despite these advancements, MCSampEn2D encounters challenges with significant errors and slow convergence rates. To counter these issues, we have incorporated an upper confidence bound (UCB) strategy in MCSampEn2D. This strategy involves assigning varied upper confidence bounds in each Monte Carlo experiment iteration to enhance the algorithm's speed and accuracy. Our evaluation of this enhanced approach, dubbed UCBMCSampEn2D, involved the use of medical and natural image data sets. The experiments demonstrate that UCBMCSampEn2D achieves a 40% reduction in computational time compared to MCSampEn2D. Furthermore, the errors with UCBMCSampEn2D are only 30% of those observed in MCSampEn2D, highlighting its improved accuracy and efficiency.
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BACKGROUND: Avian leukosis viruses (ALVs) are important contagious suppressive factors of chicken immunity and growth performance, resulted in enormous economic loss. Although virus eradication programs are applied in breeder flocks, ALVs are still widespread globally. Therefore, other valuable adjunct to reduce the negative effect of ALVs should be considered. Bursin-like peptide (BLP) showed remarkable immunomodulatory effects, whereas their influence on ALV-infected avian groups has not been reported. Here, a designed hybrid BLP was expressed in E. coli. The purified BLP was injected subcutaneously weekly in SPF chickens congenitally infected with a natural ALV strain. Then the influences of this BLP on the growth performance, immune response and virus titer of ALV-infected chickens were determined. RESULTS: This BLP injection significantly improved the body weights of ALV-infected birds (P < 0.05). BLP injection significantly enhanced organ index in the BF in ALV-infected birds (P < 0.05). The weekly injection of BLP significantly lengthened the maintenance time of antibodies against Newcastle disease virus (NDV) attenuated vaccine of ALV-infected birds (P < 0.05) and boosted the antibody titer against avian influenza virus (AIV) H5 inactive vaccine of mock chicken (P < 0.05). BLP injection in mock chickens enhanced the levels of serum cytokines (IL-2, IL-4 and interferon-γ) (P < 0.05). Surprisingly, the novel BLP significantly inhibited expression of the ALV gp85 gene in the thymus (P < 0.05), kidney (P < 0.05) and bursa of Fabricius (BF) (P < 0.01) of ALV-infected chickens. Both viral RNA copy number and protein level decreased significantly with BLP (50 µg/mL) inoculation before ALV infection in DF1 cells (P < 0.05). CONCLUSIONS: This is the first report investigating the influence of BLP on the growth and immunity performance of chickens infected by ALV. It also is the first report about the antiviral effect of BLP in vivo and in vitro. This BLP expressed in E. coli showed potential as a vaccine adjuvant, growth regulator and antiretroviral drug in chickens to decrease the negative effects of ALV infection.
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Virus de la Leucosis Aviar/efectos de los fármacos , Oligopéptidos/inmunología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/virología , Animales , Leucosis Aviar/inmunología , Peso Corporal , Línea Celular , Pollos/crecimiento & desarrollo , Escherichia coli , Virus de la Enfermedad de Newcastle/inmunología , Organismos Libres de Patógenos EspecíficosRESUMEN
The aim of the present study was to investigate effects of dietary Lactobacillus delbrueckii (L. delbrueckii) on immune response, disease resistance against Aeromonas hydrophila (A. hydrophila), antioxidant capability and growth performance of Cyprinus carpio Huanghe var. 450 fish (mean weight of 1.05 ± 0.03 g) were randomly distributed into five groups that fed diets containing different levels of L. delbrueckii (0, 1 × 105, 1 × 106, 1 × 107 and 1 × 108 CFU g-1) for 8 weeks. The results showed that intestinal immune parameters such as lysozyme, acid phosphatase, and myeloperoxidase activities, immunoglobulin M content, and the survival rate were improved in fish fed with 1 × 106 and 1 × 107 CFU g-1L. delbrueckii. In addition, 1 × 107 CFU g-1L. delbrueckii supplementation down-regulated mRNA levels of TNF-α, IL-8, IL-1ß and NF-κBp65, and up-regulated IL-10 and TGF-ß mRNA levels in the intestine. The survival rate was significantly (P < 0.05) higher (68.33%) in fish fed 1 × 106 CFU g-1L. delbrueckii than the control diet-fed group (40%) after challenge by A. hydrophila. Fish fed with diet containing 1 × 106 CFU g-1L. delbrueckii showed higher antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and total antioxidant capacity (T-AOC) and lower MDA concentrations than those of the control group (P < 0.05). The relative gene expression (SOD, CAT, GPX) showed the same trend with their activities. In addition, the growth performance was significantly improved in fish fed with the diet containing 1 × 106 and 1 × 107 CFU g-1L. delbrueckii (P < 0.05). These results demonstrated that dietary optimal levels of L. delbrueckii enhanced immunity, disease resistance against A. hydrophila antioxidant capability and growth performance in Cyprinus carpio Huanghe var.
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Carpas , Suplementos Dietéticos , Resistencia a la Enfermedad , Enfermedades de los Peces/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , Inmunidad Innata , Lactobacillus delbrueckii , Aeromonas hydrophila/fisiología , Alimentación Animal/análisis , Animales , Antioxidantes/metabolismo , Carpas/crecimiento & desarrollo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/prevención & control , Lactobacillus delbrueckii/química , Lactobacillus delbrueckii/inmunología , Distribución AleatoriaRESUMEN
Tissue regeneration is a hot topic in the field of biomedical research in this century. Material composition, surface topology, light, ultrasonic, electric field and magnetic fields (MFs) all have important effects on the regeneration process. Among them, MFs can provide nearly non-invasive signal transmission within biological tissues, and magnetic materials can convert MFs into a series of signals related to biological processes, such as mechanical force, magnetic heat, drug release, etc. By adjusting the MFs and magnetic materials, desired cellular or molecular-level responses can be achieved to promote better tissue regeneration. This review summarizes the definition, classification and latest progress of MFs and magnetic materials in tissue engineering. It also explores the differences and potential applications of MFs in different tissue cells, aiming to connect the applications of magnetism in various subfields of tissue engineering and provide new insights for the use of magnetism in tissue regeneration.
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Cell culturing is a cornerstone of tissue engineering, playing a crucial role in tissue regeneration, drug screening, and the study of disease mechanisms. Among various culturing techniques, 3D culture systems, particularly those utilizing suspended fiber scaffolds, offer a more physiologically relevant environment than traditional 2D monolayer cultures. These 3D scaffolds enhance cell growth, differentiation, and proliferation by mimicking the in vivo cellular milieu. This review focuses on the critical role of suspended fiber scaffolds in tissue engineering. We compare the effectiveness of 3D suspended fiber scaffolds with 2D culture systems, discussing their respective benefits and limitations in the context of tissue regeneration. Furthermore, we explore the preparation methods of suspended fiber scaffolds and their potential applications. The review concludes by considering future research directions for optimizing suspended fiber scaffolds to address specific challenges in tissue regeneration, underscoring their significant promise in advancing tissue engineering and regenerative medicine.
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Medicina Regenerativa , Ingeniería de Tejidos , Andamios del Tejido , Andamios del Tejido/química , Humanos , Ingeniería de Tejidos/métodos , Animales , Medicina Regenerativa/métodos , Regeneración , Diferenciación Celular , Técnicas de Cultivo de Célula/métodos , Proliferación Celular , Técnicas de Cultivo Tridimensional de Células/métodosRESUMEN
Peripheral nerve injury (PNI) seriously affects the health and life of patients, and is an urgent clinical problem that needs to be resolved. Nerve implants prepared from various biomaterials have played a positive role in PNI, but the effect should be further improved and thus new biomaterials is urgently needed. Ovalbumin (OVA) contains a variety of bioactive components, low immunogenicity, tolerance, antimicrobial activity, non-toxicity and biodegradability, and has the ability to promote wound healing, cell growth and antimicrobial properties. However, there are few studies on the application of OVA in neural tissue engineering. In this study, OVA implants with different spatial structures (membrane, fiber, and lyophilized scaffolds) were constructed by casting, electrospinning, and freeze-drying methods, respectively. The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity, and can promote vascularization, show good histocompatibility, without excessive inflammatory response and immunogenicity. The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells, while the in vivo results confirmed that OVA implants (the E5/70% and 20 kV 20 µL/min groups) could effectively regulate the growth of blood vessels, reduce the inflammatory response and promote the repair of subcutaneous nerve injury. Further on, the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α (TNF-α), phosphatidylinositide 3-kinases/protein kinase B (PI3K-Akt) signaling pathway, axon guidance, cellular adhesion junctions, and nerve regeneration in Schwann cells. The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.
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The treatment of peripheral nerve injury is a clinical challenge that tremendously affected the patients' health and life. Anisotropic topographies and electric cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, most studies just unilaterally emphasize the effect of sole topological- or electric- cue on nerve regeneration, while rarely considering the synergistic function of both cues simultaneously. In this study, a biomimetic-inspired piezoelectric topological ovalbumin/BaTiO3 scaffold that can provide non-invasive electrical stimulation in situ was constructed by combining piezoelectric BaTiO3 nanoparticles and surface microtopography. The results showed that the incorporation of piezoelectric nanoparticles could improve the mechanical properties of the scaffolds, and the piezoelectric output of the scaffolds after polarization was significantly increased. Biological evaluation revealed that the piezoelectric topological scaffolds could regulate the orientation growth of SCs, promote axon elongation of DRG, and upregulate the genes expression referring to myelination and axon growth, thus rapidly integrated chemical-mechanical signals and transmitted them for effectively promoting neuronal myelination, which was closely related to peripheral neurogenesis. The study suggests that the anisotropic surface topology combined with non-invasive electronic stimulation of the ovalbumin/BaTiO3 scaffolds possess a promising application prospect in the repair and regeneration of peripheral nerve injury.
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Compuestos de Bario , Ovalbúmina , Células de Schwann , Andamios del Tejido , Titanio , Andamios del Tejido/química , Animales , Titanio/química , Compuestos de Bario/química , Anisotropía , Ganglios Espinales/citología , Ratas , Materiales Biomiméticos/química , Regeneración NerviosaRESUMEN
The re-bridging of the deficient nerve is the main problem to be solved after the functional impairment of the peripheral nerve. In this study, a directionally aligned polycaprolactone/triiron tetraoxide (PCL/Fe3O4) fiber scaffolds were firstly prepared by electrospinning technique, and further then grafted with IKVAV peptide for regulating DRG growth and axon extension in peripheral nerve regeneration. The results showed that oriented aligned magnetic PCL/Fe3O4 composite scaffolds were successfully prepared by electrospinning technique and possessed good mechanical properties and magnetic responsiveness. The PCL/Fe3O4 scaffolds containing different Fe3O4 concentrations were free of cytotoxicity, indicating the good biocompatibility and low cytotoxicity of the scaffolds. The IKVAV-functionalized PCL/Fe3O4 scaffolds were able to guide and promote the directional extension of axons, the application of external magnetic field and the grafting of IKVAV peptides significantly further promoted the growth of DRGs and axons. The ELISA test results showed that the AP-10â¯F group scaffolds promoted the secretion of nerve growth factor (NGF) from DRG under a static magnetic field (SMF), thus promoting the growth and extension of axons. Importantly, the IKVAV-functionalized PCL/Fe3O4 scaffolds could significantly up-regulate the expression of Cntn2, PCNA, Sox10 and Isca1 genes related to adhesion, proliferation and magnetic receptor function under the stimulation of SMF. Therefore, IKVAV-functionalized PCL/Fe3O4 composite oriented scaffolds have potential applications in neural tissue engineering.
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Poliésteres , Andamios del Tejido , Animales , Poliésteres/química , Ratas , Andamios del Tejido/química , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Factor de Crecimiento Nervioso/farmacología , Factor de Crecimiento Nervioso/química , Regeneración Nerviosa/efectos de los fármacos , Campos Magnéticos , Compuestos Férricos/química , Compuestos Férricos/farmacología , Ratas Sprague-Dawley , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Células PC12RESUMEN
To quantitatively evaluate the carbon emission effects of various underground mining schemes in metal mines, a carbon emission calculation model specifically for underground metal mines was established. The carbon emissions stemming from the mine's production process were categorized into three components: carbon emissions from the production of consumed materials, fuel, and electricity; carbon emissions resulting from fuel combustion and explosive explosions, and the reduction of CO2 absorption due to the occupation of the surface industrial site. Subsequently, the carbon emission impact of underground metal mines was assessed using an example from an iron mine in Anhui Province, China. The results showed: (1) Among the underground mining processes, electricity consumption emerged as the primary source of carbon emissions. This underscores the potential for significant carbon emission reduction through the implementation of innovative electric power technologies in underground metal mines. (2) Mining methods with higher productivity showed clear advantages. They not only contribute to the reduction of carbon emissions per kiloton of ore from multiple perspectives but also led to a shorter mine lifespan and decreased CO2 absorption by woodlands occupied by the surface industrial site. Furthermore, these methods resulted in lower carbon emissions throughout the mine's lifespan. (3) Backfill mining proved to be effective in curbing tailings emissions and reducing the required area for a tailings pond. Consequently, this approach minimizes the CO2 absorption by woodlands occupied by the tailings pond.
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Dióxido de Carbono , Hierro , China , Carbono , Bosques , TecnologíaRESUMEN
In order to explore the potential environmental and safety risks of phosphogypsum-based cemented paste backfill (PCPB) in mines, aiming at the actual problems of different acidity and alkalinity of the groundwater environment where PCPB is located, the chemical solution erosion test, element concentration determination test, uniaxial compressive strength (UCS) test, and microscopic analysis test of PCPB were carried out. The effects of three different chemical solutions, HCl solution, NaOH solution, and pure water on the leaching toxicity and deformation failure characteristics of PCPB were analyzed. The kinetic equations of pH value of PCPB in the HCl and NaOH solutions, the leaching models of total P and fluoride, and the UCS erosion model of PCPB were established. The research shows that the pH value of PCPB is weak alkaline or alkalinity, when it reaches dynamic equilibrium in different chemical solutions. The leaching concentration of total P is higher than the Class III standard of surface water; the leaching concentration of fluoride is higher than the Class III standard of surface water, the Class III standard of groundwater, and the Class I standard of sewage. In the early stage of chemical solution erosion, scanning electron microscope (SEM) images show that the hydration product C-S-H gel and Aft are intertwined and firmly combined. The research results have important engineering practice and application value in mine environmental governance and safety management.
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Conservación de los Recursos Naturales , Fluoruros , Hidróxido de Sodio , Política Ambiental , AguaRESUMEN
In order to analyze the early mechanical properties and damage characteristics of phosphogypsum-based cemented backfill (PCB) under hydrochemical action, hydrochemical erosion and uniaxial compression strength (UCS) tests were carried out with HCl solution, NaOH solution, and water respectively. The damage degree is defined by taking the effective bearing area of the soluble cements of PCB under hydrochemistry action as the chemical damage variable, and the modified damage parameter α, which reflects the damage development characteristics, is introduced to construct the damage constitutive model of PCB considering chemical damage and load damage, and the theoretical model is verified with the experimental results. The results show that the damage constitutive model curves of PCB under different hydrochemical action are in good agreement with the experimental results, which verifies the correctness of the theoretical model. When the modified damage parameter α decreases from 1.0 to 0.8, the residual load-bearing capacity of PCB gradually increases, with the damage values of PCB samples in HCl solution and water gradually increasing before the peak and decreasing after the peak, while the damage values of PCB samples in NaOH solution show an overall increasing trend before and after the peak. The slope of the post peak curve of PCB decreases with increasing model parameter n. The results of the study can provide theoretical support and practical guidance for the strength design, long-term erosion deformation, and prediction of PCB in hydrochemical environment.
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Sulfato de Calcio , Fósforo , Hidróxido de Sodio , Modelos TeóricosRESUMEN
Silk fibroin (SF) as a natural polymer has a long history of application in various regenerative medicine fields, but there are still many shortcomings in silk fibroin for using as nerve scaffolds, which limit its clinical application in peripheral nerve regeneration (PNR). In this work, a multi-scale and multi-level metformin (MF)-loaded silk fibroin scaffold with anisotropic micro-nano composite topology was prepared by micromolding electrospinning for accelerating PNR. The scaffolds were characterized for morphology, wettability, mechanical properties, degradability, and drug release, and Schwann cells (SCs) and dorsal root ganglia (DRG) were cultured on the scaffolds to assess their effects on neural cell behavior. Finally, the gene expression differences of neural cells cultured on scaffolds were analyzed by gene sequencing and RT-qPCR to explore the possible signaling pathways and mechanisms. The results showed that the scaffolds had excellent mechanical properties and hydrophilicity, slow degradation rate and drug release rate, which were enough to support the repair of peripheral nerve injury for a long time. In Vitro cell experiments showed that the scaffolds could significantly promote the orientation of SCs and axons extension of DRG. Gene sequencing and RT-qPCR revealed that the scaffolds could up-regulate the expression of genes related to SCs proliferation, adhesion, migration, and myelination. In summary, the scaffolds hold great potential for promoting PNR at the micro/nano multiscale and physical/chemical levels and show promising application for the treatment of peripheral nerve injury in the future.
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Fibroínas , Metformina , Traumatismos de los Nervios Periféricos , Fibroínas/administración & dosificación , Fibroínas/química , Traumatismos de los Nervios Periféricos/terapia , Anisotropía , Conformación Proteica en Lámina beta , Animales , Ratas , Línea Celular , Metformina/administración & dosificación , Células de Schwann , Ganglios Espinales/citología , Nervio Ciático/lesionesRESUMEN
Peripheral nerve injuries (PNI) currently have limited therapeutic efficacy, and functional scaffolds have been shown to be effective for treating PNI. Ovalbumin (OVA) is widely used as a natural biomaterial for repairing damaged tissues due to its excellent biocompatibility and the presence of various bioactive components. However, there are few reports on the repair of PNI by ovalbumin. In this study, a novel bionic functionalized topological scaffold based on ovalbumin and grafted with tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide was constructed by micro-molding method and surface-biomodification technology. The scaffolds were subjected to a series of evaluations in terms of morphology, mechanics, hydrophilicity, and biocompatibility, and the related molecular mechanisms were further penetrated. The results showed that the scaffolds prepared in this study had aligned ridge/groove structure, good mechanical properties and biocompatibility, and could be used as carriers to slowly release YIGSR, which effectively promoted the proliferation, migration and elongation of Schwann Cells (SCs), and significantly up-regulated the gene expression related to proliferation, apoptosis, migration and axon regeneration. Therefore, the bionic functional topological scaffold has significant application potential for promoting peripheral nerve regeneration and provides a new therapeutic option for repairing PNI.
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Axones , Traumatismos de los Nervios Periféricos , Humanos , Ovalbúmina/metabolismo , Regeneración Nerviosa/fisiología , Células de Schwann , Péptidos/química , Traumatismos de los Nervios Periféricos/terapia , Andamios del Tejido/químicaRESUMEN
The purpose of nerve regeneration via tissue engineering strategies is to create a microenvironment that mimics natural nerve growth for achieving functional recovery. Biomaterial scaffolds offer a promising option for the clinical treatment of large nerve gaps due to the rapid advancement of materials science and regenerative medicine. The design of biomimetic scaffolds should take into account the inherent properties of the nerve and its growth environment, such as stiffness, topography, adhesion, conductivity, and chemical functionality. Various advanced techniques have been employed to develop suitable scaffolds for nerve repair. Since neuronal cells have electrical activity, the transmission of bioelectrical signals is crucial for the functional recovery of nerves. Therefore, an ideal peripheral nerve scaffold should have electrical activity properties similar to those of natural nerves, in addition to a delicate structure. Piezoelectric materials can convert stress changes into electrical signals that can activate different intracellular signaling pathways critical for cell activity and function, which makes them potentially useful for nerve tissue regeneration. However, a comprehensive review of piezoelectric materials for neuroregeneration is still lacking. Thus, this review systematically summarizes the development of piezoelectric materials and their application in the field of nerve regeneration. First, the electrical signals and natural piezoelectricity phenomenon in various organisms are briefly introduced. Second, the most commonly used piezoelectric materials in neural tissue engineering, including biocompatible piezoelectric polymers, inorganic piezoelectric materials, and natural piezoelectric materials, are classified and discussed. Finally, the challenges and future research directions of piezoelectric materials for application in nerve regeneration are proposed.
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Materiales Biocompatibles , Andamios del Tejido , Andamios del Tejido/química , Materiales Biocompatibles/química , Ingeniería de Tejidos/métodos , Medicina Regenerativa , Regeneración NerviosaRESUMEN
Oxidative stress has been considered as one of the possible mechanisms leading to the neurotoxicity of lead. One of the effective ways to prevent cellular damage after lead exposure is using antioxidants. In this paper, a novel C(60) -methionine derivate (FMD), a fullerene molecule modified with methionine, was synthesized. The protective effect of FMD on lead-exposed human SH-SY5Y neuroblastoma cells was investigated. In this research, after incubating with 500 µm Pb acetate alone for 72 h, the cells had undergone a series of biological changes including viability loss, apoptotic death, the depletion of glutathione (GSH), the peroxidation of membrane lipid and DNA damage. Pretreatment with FMD before lead exposure could improve cell survival, increase the GSH level, reduce malondialdehyde content and attenuate DNA damage without obvious toxicity. In addition, the protective effects of FMD were proven to be greater than those of other two C(60) -amino acid derivates, ß-alanine C(60) derivate and cystine C(60) derivate, which have been confirmed in our previous work to be able to protect rat pheochromocytoma PC12 cells from hydrogen dioxide-induced oxidative injuries. These observations suggest that FMD may serve as a potential antioxidative and neuroprotective agent in the prevention of lead intoxication.
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Antioxidantes/farmacología , Fulerenos/farmacología , Metionina , Neuroblastoma/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Compuestos Organometálicos/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Fulerenos/química , Glutatión/metabolismo , Humanos , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Metionina/análogos & derivados , Metionina/química , Metionina/farmacología , Neuroblastoma/metabolismo , Neuroblastoma/patología , Estrés Oxidativo/efectos de los fármacosRESUMEN
In the present study, we describe the synthesis and characterization of a novel folacin C(60) derivative. The compound was analyzed by FT-IR, (1)H NMR, (13)C NMR, LC-MS and elemental analysis. This water soluble fullerene derivative was able to scavenge both superoxide and hydroxyl radical with biocompatibility. Rat pheochromocytoma (PC12) cells treated with hydrogen peroxide underwent cytotoxicity and apoptotic death determined by MTT assay and flow cytometry analysis. As a novel derivative of C(60), the folacin C(60) derivative self-assembled to form spherical aggregates in H(2)O. Because the compound was amphiphilic, it could penetrate the cell membrane and play its distinguished role in protecting PC12 cells against hydrogen peroxide-induced cytotoxicity. The results suggest that folacin C(60) derivative has the potential to prevent oxidative stress-induced cell death without evident toxicity.
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Apoptosis/efectos de los fármacos , Ácido Fólico/farmacología , Estrés Oxidativo/efectos de los fármacos , Feocromocitoma/metabolismo , Animales , Cromatografía Liquida , Citometría de Flujo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Microscopía Electrónica de Transmisión , Células PC12 , Feocromocitoma/patología , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Oxidized glutathione C(60) derivative has been synthesized and characterized in our research. As a novel derivative of C(60), the glutathione C(60) derivative is soluble in dimethylsulfoxide, dimethylformamide and dimethylacetamide. Rat pheochromocytoma (PC12) cells are treated with hydrogen peroxide and underwent cytotoxicity; apoptotic death is determined by MTT assay, flow cytometry analysis, PI/Hoechst 33342 staining and glutathione assay. The results suggest that glutathione C(60) derivative has the potential to prevent oxidative stress-induced cell death without evident toxicity.
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Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Fulerenos/farmacología , Glutatión/análogos & derivados , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Antioxidantes/síntesis química , Apoptosis/fisiología , Bencimidazoles/química , Bioensayo , Citotoxinas/antagonistas & inhibidores , Citotoxinas/toxicidad , Dimerización , Citometría de Flujo , Fulerenos/química , Glutatión/síntesis química , Glutatión/farmacología , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/toxicidad , Estructura Molecular , Degeneración Nerviosa/tratamiento farmacológico , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/síntesis química , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Células PC12 , Ratas , Sales de Tetrazolio/químicaRESUMEN
Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities, especially neural diseases. One of the effective ways to prevent the reactive oxygen species (ROS) mediated cellular injury is dietary or pharmaceutical augmentation of free radical scavengers. In the present study, we describe the synthesis and characterization of a novel cystine C(60) derivative (CFD). The compound was analyzed by FT-IR, (1)H NMR, (13)C NMR, LC-MS and elemental analysis. It contains five cystine moieties per C(60) molecule. This water-soluble amino-fullerene derivative was able to scavenge both superoxide and hydroxyl radical with biocompatibility. We investigated its potential protective effects on hydrogen peroxide-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. Cells treated with hydrogen peroxide underwent cytotoxicity and apoptotic death determined by MTT assay, flow cytometry analysis, PI/Hoechst 33342 staining and glutathione peroxidase assay. The CFD was able to reduce the accumulation of reactive oxygen species and cellular damage caused by hydrogen peroxide in PC12 cells. RF assay demonstrated that CFD could penetrate through the cell membrane and it has played its distinguished role in protecting PC12 cells against hydrogen peroxide-induced cytotoxicity. The results suggest that CFD has the potential to prevent oxidative stress-induced cell death without evident toxicity. Hence, we can hypothesize that the protective effect of CFD on hydrogen peroxide-induced apoptosis is related to its scavenger activity.
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Apoptosis/efectos de los fármacos , Cistina/análogos & derivados , Cistina/farmacología , Fulerenos/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Ciclo Celular/efectos de los fármacos , Cistina/química , Citometría de Flujo , Colorantes Fluorescentes/química , Formazáns/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Fulerenos/química , Glutatión Peroxidasa/metabolismo , Peróxido de Hidrógeno/farmacología , Microscopía Fluorescente , Células PC12 , Ratas , Sales de Tetrazolio/químicaRESUMEN
Endocrine disruptor effects of tributyltin (TBT) are well established in fish. However, the adverse effects on lipid metabolism are less well understood. Since the liver is the predominant site of de novo synthesis of lipids, the present study uses zebrafish (Danio rerio) to examine lipid accumulation in the livers and hepatic gene expression associated with lipid metabolism pathways. After exposure for 90 days, we found that the livers in fish exposed to TBT were yellowish in appearance and with accumulation of lipid droplet, which is consistent with the specific pathological features of steatosis. Molecular analysis revealed that TBT induced hepatic steatosis by increasing the gene expression associated with lipid transport, lipid storage, lipiogenic enzymes and lipiogenic factors in the livers. Moreover, TBT enhanced hepatic caspase-3 activity and up-regulated genes related to apoptosis and cell-death, which indicated steatotic livers of fish exposed to TBT and the subsequent liver damage were likely due to accelerated hepatocyte apoptosis or cell stress. In short, TBT can produce multiple and complex alterations in transcriptional activity of lipid metabolism and cell damage, which provides potential molecular evidence of TBT on hepatic steatosis.