RESUMEN
Flowering is a key developmental transition in the plant life cycle. In temperate climates, flowering often occurs in response to the perception of seasonal cues such as changes in day-length and temperature. However, the mechanisms that have evolved to control the timing of flowering in temperate grasses are not fully understood. We identified a Brachypodium distachyon mutant whose flowering is delayed under inductive long-day conditions due to a mutation in the JMJ1 gene, which encodes a Jumonji domain-containing protein. JMJ1 is a histone demethylase that mainly demethylates H3K4me2 and H3K4me3 in vitro and in vivo. Analysis of the genome-wide distribution of H3K4me1, H3K4me2, and H3K4me3 in wild-type plants by chromatin immunoprecipitation and sequencing combined with RNA sequencing revealed that H3K4m1 and H3K4me3 are positively associated with gene transcript levels, whereas H3K4me2 is negatively correlated with transcript levels. Furthermore, JMJ1 directly binds to the chromatin of the flowering regulator genes VRN1 and ID1 and affects their transcription by modifying their H3K4me2 and H3K4me3 levels. Genetic analyses indicated that JMJ1 promotes flowering by activating VRN1 expression. Our study reveals a role for JMJ1-mediated chromatin modification in the proper timing of flowering in B. distachyon.
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Brachypodium , Flores , Regulación de la Expresión Génica de las Plantas , Histonas , Proteínas de Plantas , Brachypodium/genética , Brachypodium/fisiología , Flores/genética , Flores/fisiología , Flores/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Histonas/metabolismo , Mutación/genética , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo , Cromatina/metabolismo , Cromatina/genéticaRESUMEN
Warm ambient conditions induce thermomorphogenesis and affect plant growth and development. However, the chromatin regulatory mechanisms involved in thermomorphogenesis remain largely obscure. In this study, we show that the histone methylation readers MORF-related gene 1 and 2 (MRG1/2) are required to promote hypocotyl elongation in response to warm ambient conditions. A transcriptome sequencing analysis indicates that MRG1/2 and phytochrome interacting factor 4 (PIF4) coactivate a number of thermoresponsive genes, including YUCCA8, which encodes a rate-limiting enzyme in the auxin biosynthesis pathway. Additionally, MRG2 physically interacts with PIF4 to bind to thermoresponsive genes and enhances the H4K5 acetylation of the chromatin of target genes in a PIF4-dependent manner. Furthermore, MRG2 competes with phyB for binding to PIF4 and stabilizes PIF4 in planta. Our study indicates that MRG1/2 activate thermoresponsive genes by inducing histone acetylation and stabilizing PIF4 in Arabidopsis.
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Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Histonas , Vernalización , Arabidopsis/genética , Cromatina , Metilación , Proteínas de Arabidopsis/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Proteínas Cromosómicas no HistonaRESUMEN
Soft robotics offer unusual bioinspired solutions to challenging engineering problems. Colorful display and morphing appendages are vital signaling modalities used by natural creatures to camouflage, attract mates, or deter predators. Engineering these display capabilities using traditional light emitting devices is energy expensive and bulky and requires rigid substrates. Here, we use capillary-controlled robotic flapping fins to create switchable visual contrast and produce state-persistent, multipixel displays that are 1000- and 10-fold more energy efficient than light emitting devices and electronic paper, respectively. We reveal the bimorphic ability of these fins, whereby they switch between straight or bent stable equilibria. By controlling the droplets temperature across the fins, the multifunctional cells simultaneously exhibit infrared signals decoupled from the optical signals for multispectral display. The ultralow power, scalability, and mechanical compliance make them suitable for curvilinear and soft machines.
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Aletas de Animales , Robótica , Animales , Acción Capilar , Electrónica , IngenieríaRESUMEN
Pharmacologically-induced persistent hippocampal γ oscillation in area CA3 requires activation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs). However, we demonstrated that exogenous AMPA dose-dependently inhibited carbachol (CCH)-induced γ oscillation in the CA3 area of rat hippocampal slices, but the underlying mechanism is not clear. Application of AMPARs antagonist NBQX (1 µM) did not affect γ oscillation power (γ power), nor AMPA-mediated γ power reduction. At 3 µM, NBQX had no effect on γ power but largely blocked AMPA-mediated γ power reduction. Ca2+-permeable AMPA receptor (CP-AMPAR) antagonist IEM1460 or CaMKK inhibitor STO-609 but not CaMKIIα inhibitor KN93 enhanced γ power, indicating that activation of CP-AMPAR or CaMKK negatively modulated CCH-induced γ oscillation. Either CP-AMPAR antagonist or CaMKK inhibitor alone did not affected AMPA-mediated γ power reduction, but co-administration of IEM1460 and NBQX (1 µM) largely prevented AMPA-mediated downregulation of γ suggesting that CP-AMPARs and CI-AMPARs are involved in AMPA downregulation of γ oscillation. The recurrent excitation recorded at CA3 stratum pyramidale was significantly reduced by AMPA application. Our results indicate that AMPA downregulation of γ oscillation may be related to the reduced recurrent excitation within CA3 local neuronal network due to rapid CI-AMPAR and CP-AMPAR activation.
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Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina , Hipocampo , Animales , Ratas , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico , Modalidades de Fisioterapia , Región CA3 Hipocampal , Carbacol/farmacologíaRESUMEN
The susceptibility to trace metals and legacy POPs is different between terrestrial and marine mammals. In this study, we established the first cell line from Indo-Pacific finless porpoises and compared the cellular responses of skin fibroblast cells from Pygmy killer whales, Pantropic spotted dolphins, Indo-Pacific finless porpoises, mice, and humans following exposure to copper, methylmercury, cadmium, PCB126, PCB153, and BDE47 to better understand the interspecies sensitivities of mammals to chemical pollutants. We conducted a risk assessment by comparing no-observed effect concentrations (NOEC), lowest-observed effect concentrations (LOEC), and half maximal effective concentrations (EC50) from cell viability assays and previously reported pollutant body burdens in mammals. Based on the in vitro data, Indo-Pacific finless porpoises were more sensitive to copper and methylmercury than other mammals. PCB153 exposure reduced cell viability in all mammals except humans, while PCB126 was more potent, with 13.33 µg/mL exposure reducing cell viability in all mammals. In contrast, BDE47 exposure reduced cell viability only in terrestrial mammals in addition to pantropic spotted dolphin. Based on the in vitro data and the natural context of metal concentrations, both methylmercury and cadmium posed a higher risk to cetaceans than human, while copper posed a lower risk to cetaceans. All three legacy POPs (PCB126, PCB153, and BDE47) posed minor risk to cetaceans for short-term exposure. This study demonstrated that a species-specific in vitro model may provide more accurate information on the potential risk of pollutants to mammals. However, due to the bioamplification of POPs and their potential impact on the endocrine system and immune system of cetaceans, risk assessment with long-term exposure with more in vitro models should be further studied.
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Delfines , Contaminantes Ambientales , Compuestos de Metilmercurio , Marsopas , Oligoelementos , Contaminantes Químicos del Agua , Humanos , Animales , Ratones , Contaminantes Químicos del Agua/análisis , Compuestos de Metilmercurio/metabolismo , Cobre/toxicidad , Cobre/metabolismo , Cadmio/metabolismo , Marsopas/metabolismo , Delfines/metabolismo , Oligoelementos/toxicidad , Oligoelementos/metabolismo , Contaminantes Ambientales/metabolismo , FibroblastosRESUMEN
The gut microbiome is a unique marker for cetaceans' health status, and the microbiome composition of their skin wounds can indicate a potential infection from their habitat. Our study provides the first comparative analysis of the microbial communities from gut regions and skin wounds of an individual Indo-Pacific finless porpoise (Neophocaena phocaenoides). Microbial richness increased from the foregut to the hindgut with variation in the composition of microbes. Fusobacteria (67.51% ± 5.10%), Firmicutes (22.00% ± 2.60%), and Proteobacteria (10.47% ± 5.49%) were the dominant phyla in the gastrointestinal tract, while Proteobacteria (76.11% ± 0.54%), Firmicutes (22.00% ± 2.60%), and Bacteroidetes (10.13% ± 0.49%) were the dominant phyla in the skin wounds. The genera Photobacterium, Actinobacillus, Vibrio, Erysipelothrix, Tenacibaculum, and Psychrobacter, considered potential pathogens for mammals, were identified in the gut and skin wounds of the stranded Indo-Pacific finless porpoise. A comparison of the gut microbiome in the Indo-Pacific finless porpoise and other cetaceans revealed a possible species-specific gut microbiome in the Indo-Pacific finless porpoise. There was a significant difference between the skin wound microbiomes in terrestrial and marine mammals, probably due to habitat-specific differences. Our results show potential species specificity in the microbiome structure and a potential threat posed by environmental pathogens to cetaceans.
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Interleukin-25 (IL-25) has been recognized as a new member of the IL-17 family and implicated in various inflammatory pathology. We aimed to investigate the effects of IL-25 on the expression of matrix metalloproteinase-2 (MMP-2), MMP-8, and MMP-9 in periodontal fibroblast cells (PFCs), cell migration, cytoskeleton F-actin, and to explore the involved extracellular-regulated protein kinases (ERKs), P38 mitogen-activated protein kinase (P38MAPK) signaling pathways, and IL-17 receptor. To evaluate the expression of MMP-2, MMP-8, MMP-9, and F-actin, PFCs were treated by various doses of IL-25 (0, 20, 50, 100, and 500 ng/ml). Protein expression of extracellular metalloproteinase inducer (EMMPRIN) was also evaluated by western blot. Cell scratches experiment was performed to test the cell migration ability. ERK, P38MAPK, and Jun N-terminal kinase signal pathways and related expression of P-ERK and P-P38MAPK were examined after treatment of different doses of IL-25 and after treatment of inhibitors of ERK and P38MAPK. Immunofluorescence of MMP-2, MMP-9, and F-actin were evaluated after inhibitor treatment. IL-17RB small interfering RNA was used to examine the receptor of IL-25. IL-25 increased the protein expression of MMP-2 and MMP-9. MMP-8 and EMMPRIN expressions were not regulated by IL-25 in PFCs. Positive IF staining extended strongly from the central part to the whole cell. IL-25 mediated MMP-2, MMP-9, F-actin expressions and cell migration were regulated by P38MAPK and ERK pathways, and IL-17RB. SB203580 and U0126 blocked the effects of IL-25 through the inhibition of ERK, P38MAPK, P-ERK, and P-P38MAPK. The data indicate that IL-25 could regulate cell migration, MMP-2, and MMP-9 expression, but not MMP-8 expression, in PFCs. Moreover, the regulation effects were involved in ERK and P38MAPK pathways, and receptor IL-17RB.
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Interleucina-17/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Movimiento Celular/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Interleucina-17/fisiología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/fisiología , Metaloproteinasa 9 de la Matriz/fisiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Ligamento Periodontal/metabolismo , Cultivo Primario de Células , Transducción de Señal/efectos de los fármacos , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a major threat to public health. However, few effective therapeutic strategies exist. We aimed to identify potentially therapeutic target genes of HCC by analyzing three gene expression profiles. METHODS: The gene expression profiles were analyzed with GEO2R, an interactive web tool for gene differential expression analysis, to identify common differentially expressed genes (DEGs). Functional enrichment analyses were then conducted followed by a protein-protein interaction (PPI) network construction with the common DEGs. The PPI network was employed to identify hub genes, and the expression level of the hub genes was validated via data mining the Oncomine database. Survival analysis was carried out to assess the prognosis of hub genes in HCC patients. RESULTS: A total of 51 common up-regulated DEGs and 201 down-regulated DEGs were obtained after gene differential expression analysis of the profiles. Functional enrichment analyses indicated that these common DEGs are linked to a series of cancer events. We finally identified 10 hub genes, six of which (OIP5, ASPM, NUSAP1, UBE2C, CCNA2, and KIF20A) are reported as novel HCC hub genes. Data mining the Oncomine database validated that the hub genes have a significant high level of expression in HCC samples compared normal samples (t-test, p < 0.05). Survival analysis indicated that overexpression of the hub genes is associated with a significant reduction (p < 0.05) in survival time in HCC patients. CONCLUSIONS: We identified six novel HCC hub genes that might be therapeutic targets for the development of drugs for some HCC patients.
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Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Biología Computacional , Perfilación de la Expresión Génica , Genes Relacionados con las Neoplasias , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Terapia Molecular Dirigida , PronósticoRESUMEN
This study aimed to select the feature genes of hepatocellular carcinoma (HCC) with the Fisher score algorithm and to identify hub genes with the Maximal Clique Centrality (MCC) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to examine the enrichment of terms. Gene set enrichment analysis (GSEA) was used to identify the classes of genes that are overrepresented. Following the construction of a protein-protein interaction network with the feature genes, hub genes were identified with the MCC algorithm. The Kaplan-Meier plotter was utilized to assess the prognosis of patients based on expression of the hub genes. The feature genes were closely associated with cancer and the cell cycle, as revealed by GO, KEGG and GSEA enrichment analyses. Survival analysis showed that the overexpression of the Fisher score-selected hub genes was associated with decreased survival time (P < 0.05). Weighted gene co-expression network analysis (WGCNA), Lasso, ReliefF and random forest were used for comparison with the Fisher score algorithm. The comparison among these approaches showed that the Fisher score algorithm is superior to the Lasso and ReliefF algorithms in terms of hub gene identification and has similar performance to the WGCNA and random forest algorithms. Our results demonstrated that the Fisher score followed by the application of the MCC algorithm can accurately identify hub genes in HCC.
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Algoritmos , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Biología Computacional/métodos , Conjuntos de Datos como Asunto , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Hígado/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas/genética , Análisis de SupervivenciaRESUMEN
BACKGROUND: The aim of this study was to compare the clinical effects between traditional surgery and minimally invasive periodontal surgery in the treatment of epulis. METHODS: A total of 33 cases of patients diagnosed with fibrous epulis were randomly divided into traditional surgery group and minimally invasive periodontal surgery group. After the different procedures, several parameters were detected to evaluate the effects of minimally invasive periodontal surgery. RESULTS: Preoperative bleeding index and plaque index, adopt rank, and test showed no significant differences between the 2 groups. After 12 weeks, gingival papilla filling index in experiment group is statistically higher than control group, and shows the statistical differences (Pâ<â.05). The width of keratinized gingiva in experiment group grew more than that in control group, and showed the statistical differences (4.68â±â0.30 vs 3.00â±â0.28âmm, Pâ<â.05). No recurrence of fibrous epulis was found during the subsequent 6 months to 2 years follow-up after the surgeries. CONCLUSION: Minimally invasive periodontal surgery that reserved tumor epithelium could have a better effect than the traditional surgery in the selected patients.
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Enfermedades de las Encías/cirugía , Neoplasias Gingivales/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Dimensión del Dolor , Dolor Postoperatorio/etiología , Satisfacción del Paciente , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Drug repurposing offers a promising alternative to dramatically shorten the process of traditional de novo development of a drug. These efforts leverage the fact that a single molecule can act on multiple targets and could be beneficial to indications where the additional targets are relevant. Hence, extensive research efforts have been directed toward developing drug based computational approaches. However, many drug based approaches are known to incur low successful rates, due to incomplete modeling of drug-target interactions. There are also many technical limitations to transform theoretical computational models into practical use. Drug based approaches may, thus, still face challenges for drug repurposing task. Upon this challenge, we developed a consensus inverse docking (CID) workflow, which has a ~ 10% enhancement in success rate compared with current best method. Besides, an easily accessible web server named auto in silico consensus inverse docking (ACID) was designed based on this workflow (http://chemyang.ccnu.edu.cn/ccb/server/ACID).
RESUMEN
Structural analyses of drugs and pesticides can enable the identification of new bioactive compounds with novel and diverse scaffolds as well as improve our understanding of the bioactive fragment space. The Pesticide And Drug Fragments (PADFrag) database is a unique bioinformatic-cheminformatic cross-referencing resource that combines detailed bioactive fragment data and potential targets with a strong focus on quantitative, analytic, and molecular-scale information for the exploration of bioactive fragment space for drug discovery ( http://chemyang.ccnu.edu.cn/ccb/database/PADFrag/ ). The main applications of PADFrag are the analysis of the privileged structures within known bioactive molecules, ab initio molecule library design, and core fragment discovery for fragment-based drug design. Other potential applications include prediction of fragment interactions and general pharmaceutical research.
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Bases de Datos Factuales , Descubrimiento de Drogas , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Biología Computacional , Diseño de Fármacos , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Estructura Molecular , Programas InformáticosRESUMEN
The purposes of this study were to construct a novel tissue engineered bone composed of 3D-printed bioactive glass block/chitosan nanoparticles (BD/CSn) composites loaded with Nel-like Type I molecular-1 DNA (pDNA-NELL1) and/or bone marrow mesenchymal stem cells (BMSCs), and study their osteogenic activities by repairing bone defects in rhesus monkeys. CSn with NELL1 gene plasmid and rhesus monkey BMSCs were composited with a BD scaffold to prepare the tissue-engineered bone. Four adult female rhesus monkeys with 10- to 12-years old and 5-7 kg in weight were used in animal experiments. The first and second premolar teeth from four regions of each monkey were removed to form bone defects with size of 10 × 10 × 5 mm, which were then implanted with above-mentioned tissue engineered bone. At 12 weeks after the implantation, gross observations, X-ray and micro-CT observations revealed that the new bone was extremely close to normal bone in mass, density, hardness, and structure. The bony cortex was smooth and closely connected to the surrounding normal bone. Histological observations revealed moderate inflammation in the repair area, and the new bone tissues were similar to normal ones. In conclusion, tissue engineered bone of this study exhibited good osteoconductivity for promoting the formation of new alveolar bone tissue, and NELL1 gene played a promotional role in bone regeneration.
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OBJECTIVE: To observe the effect of hypoxia on autophagy in Beclin-1-knockdown SH-SY5Y cells by constructing a stable transfected SH-SY5Y cell lines of silencing Beclin-1 gene. METHODS: Beclin-1shRNA lentiviral vector and negative control lentiviral vector were constructed; the vector was transfected into SH-SY5Y cells; then the expression of Beclin-1 mRNA was detected by RT-PCR, the level of Beclin-1 protein was detected by Western blot. CCK-8 method was used to determine the effect of Beclin-1 knockdown on the viability of SH-SY5Y cells. Next, the blank control, negative control and transfected cells were cultured under 21% normoxia and 5% hypoxia conditions. The expression of LC3 protein in each group was detected by Western blot and the autophagic bodies were observed by electron microscopy. RESULTS: Beclin-1 shRNA significantly inhibited the expression of Beclin-1 mRNA and protein in SH-SY5Y cells; after silencing Beclin 1 gene, the survival rate of Beclin-1 shRNA group cells was no different from that of negative control (NC) group. After 5% hypoxia treatment, compared with NC group, the ratio of LC3â ¡/LC3â and the number of autophagy bodies were all decreased in Beclin-1 shRNA group. CONCLUSIONS: Beclin-1 knockdown SH-SY5Y cell lines and negative control cell lines were successfully established. Lentivirus-mediated Beclin-1 shRNA has no effect on the viability of SH-SY5Y cells, but can inhibit hypoxia-induced autophagy.
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Autofagia , Apoptosis , Beclina-1 , Hipoxia de la Célula , Línea Celular Tumoral , Humanos , ARN Interferente PequeñoRESUMEN
Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20-80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate-induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole-cell current-clamp and voltage-clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~ 50% in a concentration-dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous inhibitory post-synaptic currents, but did not affect the frequency of spontaneous excitatory post-synaptic currents. The atorvastatin-induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D-AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate-induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol-lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations.
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Anticolesterolemiantes/farmacología , Atorvastatina/farmacología , Región CA3 Hipocampal/efectos de los fármacos , Ritmo Gamma , Animales , Anticolesterolemiantes/efectos adversos , Atorvastatina/efectos adversos , Región CA3 Hipocampal/citología , Región CA3 Hipocampal/metabolismo , Región CA3 Hipocampal/fisiología , Agonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores , Potenciales Postsinápticos Inhibidores , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Interneuronas/fisiología , Ácido Kaínico/farmacología , Masculino , Inhibidores de Proteínas Quinasas/farmacología , Células Piramidales/efectos de los fármacos , Células Piramidales/metabolismo , Células Piramidales/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
Periodontal ligament (PDL) cells play an important role in wound healing of periodontal tissues. Response of PDL cells' cellular activity to high-glucose concentration levels may be the key in understanding the relationship between periodontal disease and diabetes mellitus. We studied the effect of high-glucose medium on proliferation of PDL cells in vitro. PDL cells were cultured for 1, 4, 7, 10, 14 and 17 days in normal (1100 mg/l) glucose or in high (4500 mg/l) glucose medium. The 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for proliferation was performed. In order to evaluate the osteogenetic differentiation of human PDL cells, the cells were induced with normal- or high-glucose medium for 1, 7, 14, 21 and 28 days. The results indicated that high glucose significantly inhibited proliferation of PDL cells. Concerning the mineralised nodule formation, the percentage of calcified area to total culture dish of PDL cells in high glucose level was lower than that in normal glucose medium. The increase in alkaline phosphatase activity and collagen expression could be observed in high-glucose-containing osteogenetic factor. In conclusion, high glucose improves healing of periodontal wound by inhibiting proliferation and differentiation of PDL cells, which could explain for delayed periodontal regeneration and healing in diabetic patients.
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Glucosa/administración & dosificación , Osteogénesis/efectos de los fármacos , Ligamento Periodontal/citología , Edulcorantes/administración & dosificación , Fosfatasa Alcalina/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Colágeno/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Ligamento Periodontal/metabolismo , Cicatrización de HeridasRESUMEN
Nanomaterials-mediated photothermal therapy (PTT) often suffers from the fundamental cellular defense mechanism of heat shock response which leads to therapeutic resistance of cancer cells and reduces the therapeutic efficacy. Herein, a gold nanorods (GNRs)-siRNA platform with gene silencing capability is produced to improve the PTT efficiency. After surface modification, the GNRs show the ability to deliver siRNA oligos targeting BAG3 which is an efficient gene to block the heat-shock response. The synthesized GNRs-siRNA nanoplex exhibits excellent ability in the delivery of siRNA into cancer cells with high silencing efficiency which is even better than that of commercial Lipofectamine 2000. The in vitro and in vivo studies demonstrate the ability of the GNRs-siRNA nanoplex to sensitize the cancer cells to PTT under moderate laser irradiation by down-regulating the increased BAG3 expression and enhancing apoptosis. The GNRs-siRNA mediated PTT has large potential in clinical cancer therapy due to the elimination of therapeutic resistance and enhanced photothermal therapeutic efficacy by means of gene silencing. It also suggests an efficient platform for gene delivery and controllable gene therapy.
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Silenciador del Gen , Oro/química , Hipertermia Inducida , Nanotubos , Fototerapia , ARN Interferente Pequeño/química , Línea Celular Tumoral , HumanosRESUMEN
Ideal scaffolds for tissue engineering should have the same characteristics and morphology as the tissue. However, the microstructure of many native tissues has anisotropic characteristics, and the extracellular matrix has an orderly arrangement. Thus, aligned biomimetic scaffolds, a class of directional scaffolds, were proposed and researched to further mimic the permutations of tissue. This review covers the biomaterials, technology for the aligned biomimetic scaffolds and applications in tissue engineering. The aligned biomimetic scaffolds are extremely promising for tissue engineering because they can align the directions of cell growth, affect gene expression and significantly enhance cell reprogramming efficiency.
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Materiales Biocompatibles , Materiales Biomiméticos , Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Matriz Extracelular , HumanosRESUMEN
OBJECTIVE: To investigate the protection effects of hypoxic preconditioning(HPC) on the SH-SY5Y cell injured by oxygen-glu-cose deprivation(OGD),and to discuss the possible mechanism. METHODS: SH-SY5Y cells were randomly divided into 4 groups. In normal group,the cells were cultured without OGD treatment. In HPC group,the cultured SH-SY5Y cells were treated for 5 days by intermittently ex-posing to hypoxic gas mixture (2% O2,5% CO2) for 30 min in every day. In OGD group,the culture medium was replaced by glucose-free medium and the cells were transferred to a humidified incubation chamber flushed by a gas mixture of 1% O2 and 5% CO2 for 10 h. After that, the cells were fed with glucose-supplemented medium and cultured under normoxic condition for 24 h. In HPC+OGD group,the cultured SH-SY5Y cells were treated for 5 days by intermittently exposing to hypoxic gas mixture for 30 min in each day, then the cells were given the same treatments as those in OGD group. The cell viability was assessed by MTT assay. The degree of the cell damage was evaluated by deter-mining lactate dehydrogenase (LDH) leakage. TUNEL staining were used to detect the variation of cell apoptosis. The expression of Caspase 3 and hypoxia inducible factor-1α(HIF-1α) at protein levels was examined by Western blot. RESULTS: Hypoxic preconditioning relieved the cells apoptosis,decreased the amount of LDH leakage and improved the viability of SH-SY5Y cells injured by OGD (P<0.05). Western blot showed that the expression of Caspase 3 protein in HPC+OGD group was significantly lower than that in OGD group (P<0.05); HIF-1α protein expression was significantly higher than that of OGD group (P<0.05). CONCLUSIONS: Hypoxic preconditioning has protective effect on in vitro cultured SH-SY5Y cells injured by OGD. The mechanism may be related to the increase of HIF-1a protein.
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Apoptosis , Hipoxia de la Célula , Supervivencia Celular , Caspasa 3/metabolismo , Línea Celular , Glucosa , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , OxígenoRESUMEN
Gold nanorods (AuNRs) with unique plasmonic properties in the near-infrared region have promising biomedical applications but suffer from poor in vivo clearance because of the large size. In this study, small AuNRs with a diameter of 7 nm (designated as sAuNRs) are found to have low toxicity and high clearance rates in vivo. Compared to common AuNRs with a diameter of 14 nm (designated as bAuNRs), sAuNRs exhibit similar surface plasmon resonance bands and photothermal efficiency as bAuNRs but have lower cytotoxicity as well as higher cell uptake. The in vivo biodistribution study indicates that only 0.68% of the intravenously injected sAuNRs remain in the body after 30 days, but the residual amount in the body after injection of bAuNRs is as high as 12.3%. The results demonstrate that the smaller AuNRs having lower toxicity and increased clearance in vivo have large clinical potential.