RESUMEN
Acute kidney injury (AKI) is a common clinical syndrome lacking effective pharmacotherapy. Gambogic acid (GA), as an active ingredient of herbal medicines, exhibits antioxidant and anti-inflammatory effects that benefit the treatment of AKI, but its poor aqueous solubility limits effective renal delivery. We, for the first time, developed GA-based nanoparticles (GA-NPs) with preferential renal uptake for AKI treatment. By PEGylating with NH2-PEG5000-NOTA, hydrophobic GA was self-assembled into â¼4.5 nm nanoparticles, which showed the enhanced renal accumulation in AKI models from PET images. Importantly, the in vitro cell assays and in vivo tests of the two AKI models have confirmed the obvious nephroprotective effects and biosafety of GA-NPs. Therefore, this work indicates that GA-NPs can be a promising therapeutic candidate for the management of AKI.
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Lesión Renal Aguda , Nanopartículas , Humanos , Portadores de Fármacos/química , Nanopartículas/uso terapéutico , Nanopartículas/química , Lesión Renal Aguda/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Polietilenglicoles/químicaRESUMEN
Intelligent actuating materials have drawn enormous attention because of their potential applications in soft robots, smart sensors, bionics, etc. Aiming to integrate light, thermal, and humidity stimuli deformations and self-healing function into a single polymer, a smart actuating polyurethane material CPPU-50 is designed and successfully synthesized through co-polymerization of azobenzene-containing Azo-C12 , polyethylene glycol 200 (PEG200), and 4,4'-diphenylmethane diisocyanate (MDI) at a ratio of 1:1:2. The obtained polyurethane CPPU-50 exhibits good photoinduced bending, thermal responsive shape memory effect, humidity triggered deflections and self-healing properties. Furthermore, an actuator combining light and thermal stimuli is created and the self-healing CPPU-50 film can withstand the object of 1800 times without tearing. This work can pave a way for further development of long-lived multi-stimuli-responsive actuating devices and intelligent materials.
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Poliuretanos , Materiales Inteligentes , Humedad , Biónica , Polietilenglicoles , PolímerosRESUMEN
As a global health problem, liver fibrosis still does not have approved treatment. It was proved that N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4) has anti-hepatic fibrosis activity. However, IMB16-4 displays poor water solubility and poor bioavailability. We are devoted to developing biodegraded liposome-coated polymeric nanoparticles (LNPs) as IMB16-4 delivery systems for improving aqueous solubility, cellular uptake, and anti-fibrotic effects. The physical states of IMB16-4-LNPs were analyzed using a transmission electron microscope (TEM), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimeter (DSC). The results show that IMB16-4-LNPs increased the drug loading compared to liposomes and enhanced cellular uptake behavior compared with IMB16-4-NPs. In addition, IMB16-4-LNPs could repress the expression of hepatic fibrogenesis-associated proteins, indicating that IMB16-4-LNPs exhibited evident anti-fibrotic effects.
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Liposomas , Nanopartículas , Liposomas/química , Nanopartículas/química , Polímeros/química , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Photothermal therapy has attracted extensive attentions in cancer treatment due to its precise spatial-temporal controllability, minimal invasiveness, and negligible side effects. However, two major deficiencies, unsatisfactory heat conversion efficiency and limited tissue penetration depth, hugely impeded its clinical application. In this work, hollow carbon nanosphere modified with polyethylene glycol-graft-polyethylenimine (HPP) was elaborately synthesized. The synthesized HPP owns outstanding physical properties as a photothermal agent, such as uniform core-shell structure, good biocompatibility and excellent heat conversion efficiency. Upon NIR-II laser irradiation, the intracellular HPP shows excellent photothermal activity towards cancer cell killing. In addition, depending on the large internal cavity of HPP, the extended biomedical application as drug carrier was also demonstrated. In general, the synthesized HPP holds a great potential in NIR-II laser-activated cancer photothermal therapy.
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Materiales Biocompatibles , Carbono/química , Nanosferas/química , Fototerapia/métodos , Terapia Fototérmica , Animales , Portadores de Fármacos/química , Humanos , Neoplasias/terapia , PolietilenglicolesRESUMEN
A new series of (sulfonamido)propanamides (6a1-6a13, 6b1-6b15, 7c1-7c5, 6d1-6d5, 6e1-6e6) was designed and synthesized. All the synthesized compounds were characterized by NMR and mass spectrometry. The target compounds were evaluated for their inâ vitro cytotoxic activity against hepatocellular carcinoma (HepG2), fibrosarcoma (HT-1080), mouth epidermal carcinoma (KB), and breast adenocarcinoma (MCF-7) cell lines with the sulforhodamine B (SRB) assay, with gemcitabine and mitomycin C as positive controls. Most of these compounds exhibit a more potent cytotoxic effect than the positive control group on various cancer cell lines and the most potent compound, 6a7, shows the IC50 values of 29.78±0.516â µm, 30.70±0.61â µm, and 64.89±3.09â µm in HepG2, HT-1080, KB, and MCF-7â cell lines, respectively. Thus, these compounds with potent cytotoxic activity have potential for development as new chemotherapy agents.
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Antineoplásicos/farmacología , Diseño de Fármacos , Propionatos/farmacología , Sulfonamidas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Propionatos/síntesis química , Propionatos/química , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/químicaRESUMEN
Plant MYB transcription factors control diverse biological processes, such as differentiation, development and abiotic stress responses. In this study, we characterized BplMYB46, an MYB gene from Betula platyphylla (birch) that is involved in both abiotic stress tolerance and secondary wall biosynthesis. BplMYB46 can act as a transcriptional activator in yeast and tobacco. We generated transgenic birch plants with overexpressing or silencing of BplMYB46 and subjected them to gain- or loss-of-function analysis. The results suggest that BplMYB46 improves salt and osmotic tolerance by affecting the expression of genes including SOD, POD and P5CS to increase both reactive oxygen species scavenging and proline levels. In addition, BplMYB46 appears to be involved in controlling stomatal aperture to reduce water loss. Overexpression of BplMYB46 increases lignin deposition, secondary cell wall thickness and the expression of genes in secondary cell wall formation. Further analysis indicated that BplMYB46 binds to MYBCORE and AC-box motifs and may directly activate the expression of genes involved in abiotic stress responses and secondary cell wall biosynthesis whose promoters contain these motifs. The transgenic BplMYB46-overexpressing birch plants, which have improved salt and osmotic stress tolerance, higher lignin and cellulose content and lower hemicellulose content than the control, have potential applications in the forestry industry.
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Betula/genética , Pared Celular/química , Pared Celular/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Factores de Transcripción/genética , Arabidopsis/genética , Muerte Celular , Núcleo Celular , Celulosa/metabolismo , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Vectores Genéticos , Lignina/metabolismo , Cebollas/citología , Cebollas/genética , Presión Osmótica , Proteínas de Plantas/genética , Estomas de Plantas/genética , Estomas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Polisacáridos/metabolismo , Unión Proteica , Especies Reactivas de Oxígeno/metabolismo , Tolerancia a la Sal/genética , Cloruro de Sodio/metabolismo , Estrés Fisiológico/genética , Activación Transcripcional/genética , Agua , Xilema/citología , Xilema/genéticaRESUMEN
In this work, a facile aqueous synthesis method is optimized to produce Mn:ZnSe/ZnS/ZnMnS sandwiched quantum dots (SQDs). In this core-shell co-doped system, paramagnetic Mn(2+) ions are introduced as core and shell dopants to generate Mn phosphorescence and enhance the magnetic resonance imaging signal, respectively. T1 relaxivity of the nanoparticles can be improved and manipulated by raising the shell doping level. Steady state and time-resolved optical measurements suggest that, after high level shell doping, Mn phosphorescence of the core can be sustained by the sandwiched ZnS shell. Because the SQDs are free of toxic heavy metal compositions, excellent biocompatibility of the prepared nanocrystals is verified by in vitro MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To explore the theranostic applications of SQDs, liposome-SQD assemblies are prepared and used for ex vivo optical and magnetic resonance imaging. In addition, these engineered SQDs as nanocarrier for gene delivery in therapy of Panc-1 cancer cells are employed. The therapeutic effects of the nanocrystals formulation are confirmed by gene expression analysis and cell viability assay.
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Compuestos de Manganeso/química , Manganeso/química , Imagen Multimodal/métodos , Puntos Cuánticos/química , Compuestos de Selenio/química , Sulfuros/química , Nanomedicina Teranóstica/métodos , Compuestos de Zinc/química , Línea Celular Tumoral , Humanos , Hidrodinámica , Liposomas , Luminiscencia , Imagen por Resonancia Magnética , Microscopía Fluorescente , Sondas Moleculares/química , Tamaño de la Partícula , Puntos Cuánticos/ultraestructura , ARN Interferente Pequeño/metabolismo , Espectrofotometría Ultravioleta , TransfecciónRESUMEN
Betula platyphylla Suk (birch) is an excellent short-term hardwood species with growth and wood characteristics well suited to wood industries. To investigate the molecular mechanism of wood development in birch, a tension wood (TW) induced system was used to explore the regulatory mechanism at the protein level and identify the key proteins involved in xylem development in birch. The results of dyeing with Safranin O-Fast Green indicated that the cellulose content of TW was significantly higher than that of opposite wood (OW) or normal wood (NW), and the lignin content in TW was significantly lower than that in OW and NW after artificial bending of birch stems. Protein profile analysis of TW, NW and OW by iTRAQ revealed that there were 639 and 460 differentially expressed proteins (DEPs) between TW/OW and TW/NW, respectively. The DEPs were mainly enriched in tyrosine metabolism, glycolysis/gluconeogenesis, phenylalanine and tyrosine metabolism, phenylpropanoid and pyruvate metabolism, the pentose phosphate pathway, the citrate cycle (TCA cycle), fructose and mannose metabolism, carbon fixation in photosynthetic organisms, fatty acid biosynthesis, photosynthesis proteins and other pathways. The proteins in the citrate cycle were upregulated. The expression levels of PGI, PGM and FRK proteins related to cellulose synthesis increased and the expression levels of PAL, 4CL and COMT related to lignin synthesis decreased, leading to an increase in cellulose content and decreased lignin levels in TW. PPI analysis revealed that key DEPs interact with each other, indicating that these proteins form complexes to implement this function, which may provide important insights for wood formation at the molecular level.
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Lignina , Madera , Lignina/metabolismo , Celulosa/metabolismo , Betula , Citratos/metabolismo , Tirosina/metabolismoRESUMEN
BACKGROUND: Antimicrobial blue light (aBL) kills a variety of bacteria, including Porphyromonas gingivalis. However, little is known about the transcriptomic response of P. gingivalis to aBL therapy. This study was designed to evaluate the selective cytotoxicity of aBL against P. gingivalis over human cells and to further investigate the genetic response of P. gingivalis to aBL at the transcriptome level. METHODS: Colony forming unit (CFU) testing, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to investigate the antimicrobial effectiveness of blue light against P. gingivalis. The temperatures of the irradiated targets were measured to prevent overheating. Multiple fluorescent probes were used to quantify reactive oxygen species (ROS) generation after blue-light irradiation. RNA sequencing (RNA-seq) was used to investigate the changes in global gene expression. Following the screening of target genes, real-time quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the regulation of gene expression. RESULTS: A 405 nm aBL at 100 mW/cm2 significantly killed P. gingivalis within 5 min while sparing human gingival fibroblasts (HGFs). No obvious temperature changes were detected in the irradiated surface under our experimental conditions. RNA-seq showed that the transcription of multiple genes was regulated, and RT-qPCR revealed that the expression levels of the genes RgpA and RgpB, which may promote heme uptake, as well as the genes Ftn and FetB, which are related to iron homeostasis, were significantly upregulated. The expression levels of the FeoB-2 and HmuR genes, which are related to hydroxyl radical scavenging, were significantly downregulated. CONCLUSIONS: aBL strengthens the heme uptake and iron export gene pathways while reducing the ROS scavenging pathways in P. gingivalis, thus improving the accumulation of endogenous photosensitizers and enhancing oxidative damage to P. gingivalis.
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Color , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Hierro , Luz , Porfirinas , Porphyromonas gingivalis , Porfirinas/metabolismo , Hierro/metabolismo , Porphyromonas gingivalis/citología , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/efectos de la radiación , Transporte Biológico/genética , Transporte Biológico/efectos de la radiación , Humanos , Encía/citología , Fibroblastos/citología , Fibroblastos/efectos de la radiación , Radical Hidroxilo/metabolismo , Hemo/metabolismo , Regulación hacia Arriba/efectos de la radiación , Homeostasis/efectos de la radiación , Regulación hacia Abajo/efectos de la radiación , Viabilidad Microbiana/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Aerobiosis , Genes Bacterianos/efectos de la radiación , Regulación Bacteriana de la Expresión Génica/genética , Regulación Bacteriana de la Expresión Génica/efectos de la radiaciónRESUMEN
Peroxiredoxins (Prxs) are a recently discovered family of antioxidant enzymes that catalyze the reduction of peroxides and alkyl peroxides. In this study, four Prx genes (named as ThPrxII, ThPrxIIE, ThPrxIIF, and Th2CysPrx) were cloned from Tamarix hispida. Their expression profiles in response to stimulus of NaCl, NaHCO(3), PEG, CdCl(2) and abscisic acid (ABA) in roots, stems and leaves of T. hispida were investigated using real-time RT-PCR. The results showed that the four ThPrxs were all expressed in roots, stems and leaves. Furthermore, the transcript levels of ThPrxIIE and ThPrxII were the lowest and the highest, respectively, in all tissue types. All the ThPrx genes were induced by both NaCl and NaHCO(3) and reached their highest expression levels at the onset of stress in roots. Under PEG and CdCl(2) stress, the expression patterns of these ThPrxs showed temporal and spatial specificity. The expressions of the ThPrxs were all differentially regulated by ABA, indicating that they are all involved in the ABA signaling pathway. These findings reveal a complex regulation of Prxs that is dependent on the type of Prx, tissue, and the signaling molecule. The divergence of the stress-dependent transcriptional regulation of the ThPrx gene family in T. hispida may provide an essential basis for the elucidation of Prx function in future work.
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Ácido Abscísico/farmacología , Peroxirredoxinas/biosíntesis , Peroxirredoxinas/genética , Estrés Fisiológico , Tamaricaceae/efectos de los fármacos , Secuencia de Aminoácidos , Antioxidantes , Cloruro de Cadmio/farmacología , Clonación Molecular , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Datos de Secuencia Molecular , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Tallos de la Planta/metabolismo , Polietilenglicoles/farmacología , Señales de Clasificación de Proteína/genética , Alineación de Secuencia , Bicarbonato de Sodio/farmacología , Cloruro de Sodio/farmacología , Tamaricaceae/genéticaRESUMEN
The tail of the reservoir is the unstable zone regarding water quality and phytoplankton community. Therefore, it is the crucial zone in aquatic ecosystem transitions. To understand the transition characteristics and driving mechanisms of water environment dynamics, high-frequency monitoring of the water environment and phytoplankton community in the tail of a deep and large reservoir, the Xin'anjiang Reservoir in southeast of China, was conducted using a water quality monitoring buoy and three-day interval water sampling during 18 months. Results show clear seasonal thermal and oxygen stratification in the river mouth of the reservoir. The nutrient and chlorophyll-a concentrations also show stratifying phenomena during the thermal stratification period. Heavy rain and inflow quickly consume the stratification. Nutrient concentrations were highly dynamic in the river mouth. The total phosphorus ranges from 0.011 mg·L-1 to 0.188 mg·L-1, and total nitrogen ranges from 0.75 mg·L-1 to 2.76 mg·L-1. Dissolved phosphorus comprised 56% of total phosphorus, and dissolved nitrogen occupied 88% of total nitrogen, respectively. Nutrient concentrations were influenced strongly by rainfall intensity and inflow rate. Total phosphorus and nitrogen concentrations were significantly related to the three-day accumulated rainfall. Nutrient concentrations in the flood season (March to June) were significantly higher than in the non-flood season (P<0.001). Seasonal phytoplankton proliferation also significantly influenced by total phosphorus concentration. The phytoplankton community changes significantly with seasons and flood events. Bacillariophytea was generally dominant throughout the year, with the predominant genus of Fragilaria spp., Cyclotella spp., Synedra spp., and Melosira spp. Cyanophyta biomass peaked in July, August, and September, with the dominant genus of Aphanizomenon spp., Microcystis spp., and Oscillatoria spp. Apart from the high temperature, storm inflow events also triggered Cyanophyta proliferation. The proliferation of Chlorophyta was similar to Cyanophyta, with the predominant genus of Pediastrum spp. and Closterium spp.. While the Cryptophyta biomass peaked during March to May, with the predominant genus of Cryptomonas spp.. Redundancy analysis shows that the influence factors of phytoplankton community dynamics include the inflow rate, temperature, water level, water transparency, total nitrogen, total phosphorus, and nitrogen to phosphorus ratio. The meteorological and hydrological factors were major factors for phytoplankton dynamics during later autumn and winter, while the nutrient will be the co-driving factors of phytoplankton community dynamics during summer and early autumn. The research confirmed the huge influence of the intensity rainfall event on the water environment in reservoirs and described the key environmental conditions for phytoplankton community dynamics. The research is useful for the design of the monitoring and forecasting system for water safety in drinking water source reservoirs.
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Fitoplancton/clasificación , Ríos , Calidad del Agua , China , Ecosistema , Monitoreo del Ambiente , Nitrógeno/análisis , Fósforo/análisis , Estaciones del AñoRESUMEN
Plant lipid transfer proteins (LTPs) are ubiquitous lipid-binding proteins that are involved in various stress responses. In this study, we cloned 14 unique LTP genes (ThLTP 1-14) from Tamarix hispida Willd. (Tamaricaceae) to investigate their roles under various abiotic stress conditions. The expression profiles of the 14 ThLTPs in response to NaCl, polyethylene glycol (PEG), NaHCO(3), CdCl(2) and abscisic acid (ABA) exposure in root, stem and leaf tissues were investigated using real-time RT-PCR. The results showed that all 14 ThLTPs were expressed in root, stem and leaf tissues under normal growth conditions. However, under normal growth conditions, ThLTP abundance varied in each organ, with expression differences of 9000-fold in leaves, 540-fold in stems and 3700-fold in roots. These results indicated that activity and/or physiological importance of these ThLTPs are quite different. Differential expression of the 14 ThLTPs was observed (> 2-fold) for NaCl, PEG, NaHCO(3) and CdCl(2) in at least one tissue indicating that they were all involved in abiotic stress responses. All ThLTP genes were highly induced (> 2-fold) under ABA treatment in roots, stems and/or leaves, and particularly in roots, suggesting that ABA-dependent signaling pathways regulated ThLTPs. We hypothesize that ThLTP expression constitutes an adaptive response to abiotic stresses in T. hispida and plays an important role in abiotic stress tolerance.
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Proteínas Portadoras/genética , Proteínas de Plantas/genética , Estrés Fisiológico , Tamaricaceae/genética , Ácido Abscísico/farmacología , Secuencia de Aminoácidos , Cloruro de Cadmio/farmacología , Proteínas Portadoras/metabolismo , Clonación Molecular , Biología Computacional , Etiquetas de Secuencia Expresada , Biblioteca de Genes , Datos de Secuencia Molecular , Filogenia , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Tallos de la Planta/efectos de los fármacos , Tallos de la Planta/genética , Tallos de la Planta/metabolismo , Polietilenglicoles/farmacología , Alineación de Secuencia , Transducción de Señal , Bicarbonato de Sodio/farmacología , Cloruro de Sodio/farmacología , Tamaricaceae/efectos de los fármacos , Tamaricaceae/metabolismoRESUMEN
Three-dimensional (3D) printing has great potential for establishing a ubiquitous service in the medical industry. However, the planning, optimization, and control of a ubiquitous 3D printing network have not been sufficiently discussed. Therefore, this study established a collaborative and ubiquitous system for making dental parts using 3D printing. The collaborative and ubiquitous system split an order for the 3D printing facilities to fulfill the order collaboratively and forms a delivery plan to pick up the 3D objects. To optimize the performance of the two tasks, a mixed-integer linear programming (MILP) model and a mixed-integer quadratic programming (MIQP) model are proposed, respectively. In addition, slack information is derived and provided to each 3D printing facility so that it can determine the feasibility of resuming the same 3D printing process locally from the beginning without violating the optimality of the original printing and delivery plan. Further, more slack is gained by considering the chain effect between two successive 3D printing facilities. The effectiveness of the collaborative and ubiquitous system was validated using a regional experiment in Taichung City, Taiwan. Compared with two existing methods, the collaborative and ubiquitous 3D printing network reduced the manufacturing lead time by 45% on average. Furthermore, with the slack information, a 3D printing facility could make an independent decision about the feasibility of resuming the same 3D printing process locally from the beginning.
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OBJECTIVE: This study applied the direct orthodontic force system to explore the applicability of the finite element method in the simulation of alveolar bone absorption and analyze periodontal stress distribution and the overall displacement trend. METHODS: The horizontal balanced alveolar bones of model 2, 3 and 4 were reduced by 2, 4, and 6 mm by deleting elements in reference to the established height of the normal alveolar bone model 1. Then, stress distribution on the posterior set of teeth and initial total tooth displacement under the simulated load of 1.47 N of orthodontic force were investigated. RESULTS: The total displacement of posterior teeth increased and parodontium Von Mises stress gradually increased as the alveolar bone height decreased. The total displacement trend and parodontium stress drastically increased when alveolar bone absorp-tion reached the height of 4 mm. CONCLUSIONS: When treating patients with alveolar bone loss, stress should be avoided or drasti-cally reduced to prevent irreversible damage to periodontal tissue and to improve the quality of medical treatment.
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Diente Canino , Técnicas de Movimiento Dental , Simulación por Computador , Análisis de Elementos Finitos , Humanos , Maxilar , Ligamento PeriodontalRESUMEN
The full length cDNA of a novel metallothionein (LbMT2) gene was cloned from a cDNA library of Limonium bicolor. The LbMT2 gene cloned is 518 bp in length, which includes a 64 bp of 5' untranslated region (UTR) and a 205 bp of 3' untranslated region. This gene has an open reading frame (ORF) of 249 bp in length, encoding a protein of 82 amino acid residues with the molecular mass of 8.1 kDa and theoretical pI of 4.71. The expression of LbMT2 gene in L. bicolor in response to CuSO4, CdCl2, NaCl, cold, and PEG was further investigated using real time quantitative PCR. In both leaf and root of L. bicolor, the expression of LbMT2 was induced by CuSO4, CdCl2, NaCl, and cold, but inhibited by PEG stress. LbMT2 gene was inserted into a prokaryotic expression vector (pGEX-4T-2) to produce the recombinant expression vector pGEX-LbMT2. The expression of LbMT2 in E. coli BL21 was induced with IPTG, which produced a protein band with expected size of 35 kDa on SDS-PAGE.
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Clonación Molecular/métodos , Metalotioneína/genética , Metalotioneína/metabolismo , Plumbaginaceae/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cloruro de Cadmio/farmacología , Sulfato de Cobre/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/genética , Metalotioneína/química , Datos de Secuencia Molecular , Plumbaginaceae/efectos de los fármacos , Polietilenglicoles/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Cloruro de Sodio/farmacologíaRESUMEN
OBJECTIVE: This study aims to analyze the relationship between the central incisor crown inclination and occlusal relationship via three-dimensional study. METHODS: Ten Chinese volunteers with normal occlusion were selected from physical examination of college students. Lateral cephalograms and CT scans were taken, and the CT data were imported into Simplant pro 11.04 to reconstruct three-dimensional model. In the three-dimensional model, every tooth was separated independently. The upper and lower central incisors were moved labial inclination(up) or lingual inclination(down) and then the upper and lower tooth were aligned based on the central incisor's position according to the principles of Andrew's six keys. Four groups were set up with different changes of central incisors. The upper and the lower arch were aligned again based on the moved central incisors. After every motion, the mesio-distal distances of upper and lower canines and first molars were recorded. All data were analyzed using t-test via SPSS19.0, and the significance level was set at 5%. RESULTS: The results showed that the mesio-distal distances of occlusal relationship were different from normal occlusal relations, when either upper incisor crown inclination or lower incisor crown inclination was changed, and both upper and lower incisor crown inclination were moved in same or opposite direction. According to the statistical analysis, there was no significant difference when the changes of U1-L1 were no more than 10° (Pâ¯>â¯0.05). But there was statistically significant difference (Pâ¯<â¯0.05) when changes of U1-L1 were more than 20°. CONCLUSIONS: The incisor crown inclination has influence on the establishment of occlusal relationships. The bigger difference upper and lower incisor crown inclination has, the more deviations from the normal occlusal relationship exist.
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Oclusión Dental , Imagenología Tridimensional/métodos , Incisivo/anatomía & histología , Tomografía Computarizada por Rayos X/métodos , Corona del Diente/anatomía & histología , Adolescente , Adulto , Puntos Anatómicos de Referencia , Cefalometría , Femenino , Humanos , Incisivo/diagnóstico por imagen , Incisivo/fisiología , Masculino , Maloclusión/diagnóstico por imagen , Modelos Dentales , Diente Molar , Ortodoncia , Corona del Diente/diagnóstico por imagen , Corona del Diente/fisiología , Voluntarios , Adulto JovenRESUMEN
First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro transfection results from BCPV-siRNA, a newly developed biodegradable transfection agent, BCPV, is being probed for transfection performance in an animal model.
Asunto(s)
Proteínas de Fusión bcr-abl/genética , Técnicas de Silenciamiento del Gen , Vectores Genéticos , ARN Interferente Pequeño , Transfección , Apoptosis , Humanos , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva , PoliésteresRESUMEN
In this work, we demonstrate the use of manganese doped zinc selenide QDs (Mn:ZnSe d-dots) for gene delivery in vitro. Specifically, the d-dots were prepared as nanoplexes for facilitating the intracellular delivery of small interfering RNA (siRNA) molecules to pancreatic cancer cells (Panc-1), thereby inducing sequence-specific silencing of oncogenic K-Ras mutations in pancreatic carcinoma. For nanoplex preparation, a layer-by-layer (LBL) assembling method was adopted to modify the d-dot surface with cationic polymer poly(allylamine hydrochloride) (PAH) or polyethylenimine (PEI) for generating positive surface potential for complexing with K-Ras siRNA molecules. Owing to the unique and stable PL properties of the d-dots, siRNA transfection and the subsequent intracellular release profile from the d-dot/polymer-siRNA nanoplexes were monitored by fluorescence imaging. Quantitative results from flow cytometry study suggested that a high gene transfection efficiency was achieved. The expression of the mutant K-Ras mRNA in Panc-1 cells was observed to be significantly suppressed upon transfecting them with the nanoplex formulation. More importantly, cell viability studies showed that the d-dot/PAH nanoplexes were biocompatible and non-toxic even at concentrations as high as 160 µg mL(-1). Furthermore, the amine-terminated surface could be further modified to obtain multiple bio-functions. Based on these results, we envision that the designed d-dot nanoplexes can be developed as a flexible nanoplatform for both fundamental and practical clinical research applications.
Asunto(s)
Terapia Genética/métodos , Manganeso/química , Neoplasias Pancreáticas/genética , Poliaminas/química , Puntos Cuánticos/química , ARN Interferente Pequeño/genética , Compuestos de Selenio/química , Compuestos de Zinc/química , Línea Celular Tumoral , Silenciador del Gen , Técnicas de Transferencia de Gen , Humanos , Neoplasias Pancreáticas/química , Polietileneimina/química , Polietileneimina/metabolismo , ARN Interferente Pequeño/química , TransfecciónRESUMEN
Betula platyphylla Suk (birch) is a fast-growing woody species that is important in pulp industries and the biofuels. However, as an important pulp species, few studies had been performed on its wood formation. In the present study, we investigated the molecular responses of birch xylem to artificial bending and gravitational stimuli. After trunks of birch trees were subjected to bending for 8 weeks, the cellulose content was significantly greater in tension wood (TW) than in opposite wood (OW) or normal wood (NW), whereas the lignin content in TW was significantly lower than that in OW and NW. In addition, TW grew more rapidly than OW and generated TW-specific fibers with an additional G-layer. Three transcriptome libraries were constructed from TW, OW and NW of B. platyphylla, respectively, after the plants were subjected to artificial bending. Overall, 80,909 nonredundant unigenes with a mean size of 768 nt were assembled. Expression profiles were generated, and 9,684 genes were found to be significantly differentially expressed among the TW, OW and NW libraries. These included genes involved in secondary cell wall structure, wood composition, and cellulose or lignin biosynthesis. Our study showed that during TW formation, genes involved in cellulose synthesis were induced, while the expression of lignin synthesis-related genes decreased, resulting in increased cellulose content and decreased lignin levels in TW. In addition, fasciclin-like arabinogalactan proteins play important role in TW formation. These findings may provide important insights into wood formation at the molecular level.
Asunto(s)
Betula/crecimiento & desarrollo , Betula/genética , Transcriptoma/genética , Xilema/metabolismo , Secuencia de Bases , Betula/metabolismo , Fenómenos Biomecánicos , Celulosa/metabolismo , China , Perfilación de la Expresión Génica , Biblioteca de Genes , Gravitación , Lignina/metabolismo , Datos de Secuencia Molecular , Análisis de Secuencia de ARN , Estrés Mecánico , Xilema/fisiologíaRESUMEN
Basic leucine zipper proteins (bZIPs) are transcription factors that bind abscisic acid (ABA)-responsive elements (ABREs) and enable plants to withstand adverse environmental conditions. In the present study, a novel bZIP gene, ThbZIP1 was cloned from Tamarix hispida. Expression studies in T. hispida showed differential regulation of ThbZIP1 in response to treatment with NaCl, polyethylene glycol (PEG) 6000, NaHCO(3), and CdCl(2), suggesting that ThbZIP1 is involved in abiotic stress responses. To identify the physiological responses mediated by ThbZIP1, transgenic tobacco plants overexpressing exogenous ThbZIP1 were generated. Various physiological parameters related to salt stress were measured and compared between transgenic and wild type (WT) plants. Our results indicate that overexpression of ThbZIP1 can enhance the activity of both peroxidase (POD) and superoxide dismutase (SOD), and increase the content of soluble sugars and soluble proteins under salt stress conditions. These results suggest that ThbZIP1 contributes to salt tolerance by mediating signaling through multiple physiological pathways. Furthermore, ThbZIP1 confers stress tolerance to plants by enhancing reactive oxygen species (ROS) scavenging, facilitating the accumulation of compatible osmolytes, and inducing and/or enhancing the biosynthesis of soluble proteins.