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
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
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
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
This study aimed to establish a model of synaptic plasticity by the activation of metabotropic glutamate receptor (mGluR) I in rat medial septal diagonal band (MSDB). Electrophysiological experiment was performed to record the theta frequency oscillation activities in rat MSDB slices. The data were recorded and analyzed with Spike 2 (CED, Cambridge, UK). Application of aminocyclopentane-1, 3-dicarboxylic acid (ACPD) to MSDB slices produced theta frequency oscillations (4-12 Hz) which persisted for hours after ACPD washout, suggesting the existence of a form of synaptic plasticity in long-term oscillations (LTOs). Addition of NMDA receptor antagonist AP5 (50 µM) caused no significant change in area power. In contrast, AMPA/Kainate receptor antagonist NBQX administration partially reduced the area power. Infusion of ZD7288, a hyperpolarization-activated channel (Ih) inhibitor, caused additional reduction to control level. Comparable effects were also observed with administration of DHPG (3, 5-dihydroxyphenylglycine) which also elicited LTOs. mGluR I activation induced theta oscillation and this activity maintained hours after drug washout. Both AMPA and hyperpolarization-activated channel make an essential contribution to LTO. Our study herein established a model of synaptic plasticity.
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Plasticidad Neuronal , Receptores de Glutamato Metabotrópico/fisiología , Núcleos Septales/fisiología , Ritmo Teta , Animales , Encéfalo/fisiología , Masculino , Modelos Neurológicos , Ratas , Ratas WistarRESUMEN
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
AIM: This study aimed to examine the role of the nicotinic receptor (nAChR) in the generation of theta oscillations (4-12 Hz) in vitro. METHODS: Electrophysiological studies were performed on medial septal diagonal band area (MSDB) slices to measure theta oscillation. Immunofluorescence and confocal microscopy studies were carried out to detect α4 nAChR and ß2 nAChR subunits in perfused-fixed tissue from VGluT2-GFP and GAD67-GFP transgenic mice. RESULTS: Application of nicotine to MSDB slices produced persistent theta oscillations in which area power increased in a dose-responsive manner. This activity was inhibited by GABAA receptor antagonists and partially by ionotropic glutamate receptor antagonists, indicating the involvement of local GABAergic and glutamatergic neurons in the production of the rhythmic activity. The nicotine-induced theta activity was also inhibited selectively by non-α7*nAChR antagonists, suggesting the presence of these receptor types on GABAergic and glutamatergic neuron populations in the MSDB. This was confirmed by immunofluorescence and confocal microscopy studies in transgenic mice in which the GABAergic and glutamatergic neurons express green fluorescent protein (GFP), showing localisation of ß2 nAChR and α4 nAChR subunits, the most common constituents of non-α7*nAChRs, in both cell types in the MSDB. CONCLUSION: Theta activity in the MSDB may be generated by tonic stimulation of non-α7*nAChRs.
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Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Receptores Nicotínicos/administración & dosificación , Ritmo Teta/fisiología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Técnica del Anticuerpo Fluorescente , Proteínas Fluorescentes Verdes/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Confocal , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Ratas , Ratas Wistar , Receptores Nicotínicos/efectos de los fármacos , Receptores Nicotínicos/metabolismo , Núcleos Septales/metabolismo , Ritmo Teta/efectos de los fármacosRESUMEN
A novel in vivo fluorescence spectroscopic diagnostic method has been developed in an animal model to make a quantified precancer diagnosis. In the study, 40 golden hamsters were randomly divided into four groups (groups A, B, C, and D), with group A being the control group and the other three groups being inducted at different precancer stages. A 1% Rose Bengal (RB) solution was used for the fluorescence spectroscopic diagnosis. A parameter K defined as K = I(RB)/I(auto) was introduced to reflect the amount of RB in the tissue, where I(RB) and I(auto) represent the fluorescence peak intensity of the RB in the tissue and the autofluorescence intensity of tissue at 580 nm, respectively. The average K values of the four groups were calculated and statistically analyzed by analysis of variance (ANOVA), which revealed statistically significant differences within each group as well as between groups (p < 0.001). After analysis by Clementine 11.1 C&R Tree modeling (CART), the following diagnostic criteria were set: normal, K ≤ 8.91; simple hyperplasia, 8.91 < K ≤ 41.92; mild dysplasia, 41.92 < K ≤ 70.79; moderate and severe dysplasia, K >70.79. The sensitivity and specificity to detect precancerous lesions compared with scalpel biopsy were calculated. The results of this study showed that the spectrofluorometric method mediated by RB could accurately discriminate different precancer stages.
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Neoplasias de la Boca/diagnóstico , Lesiones Precancerosas/diagnóstico , Espectrometría de Fluorescencia/métodos , Análisis de Varianza , Animales , Cricetinae , Modelos Animales de Enfermedad , Neoplasias de la Boca/patología , Lesiones Precancerosas/patología , Distribución Aleatoria , Rosa BengalaRESUMEN
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
Cyclic stretch increases Na(+)/K(+)-ATPase activity and abundance in several tissues, including skeletal muscle cells. The present study was undertaken to investigate whether Na(+)/K(+)-ATPase undergoes acute changes in its catalytic activity in response to cyclic stretch. Na(+)/K(+)-ATPase activity increased after continuously stretched for 6 h, and reached the maximum at 24 h. The inhibition of gene transcription (actinomycin D) had no effect on stretch-induced Na(+)/K(+)-ATPase activity. Cyclic stretch also increases the plasma membrane content of α(1)- and α(2)-subunit of Na(+)/K(+)-ATPase. Brefeldin A could completely abolished the stretch-induced recruitment of α-subunits to the plasma membrane and Na(+)/K(+)-ATPase activity. In conclusion, cyclic stretch directly stimulates Na(+)/K(+)-ATPase activity in skeletal muscle cells through post-transcriptional activation, likely by increasing translocation of Na(+)/K(+)-ATPase molecules to plasma membrane.
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Membrana Celular/enzimología , Fibras Musculares Esqueléticas/enzimología , Subunidades de Proteína/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Fenómenos Biomecánicos , Brefeldino A/farmacología , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/fisiología , Músculo Esquelético/citología , Subunidades de Proteína/genética , Transporte de Proteínas/efectos de los fármacos , Ratas , ATPasa Intercambiadora de Sodio-Potasio/genética , Estrés Fisiológico , Transcripción GenéticaRESUMEN
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.
RESUMEN
BACKGROUND AND OBJECTIVE: CypA is able to regulate inflammatory responses and MMPs production via interaction with its cell surface receptor, EMMPRIN. This study aimed to address the possible association of CypA with pathological inflammation and destruction of periodontal tissues, and whether CypA-EMMPRIN interaction exists in periodontitis. MATERIALS AND METHODS: Experimental periodontitis was induced by ligation according to our previous method. Histological and radiographic examinations were performed. Western blot was used to detect CypA and EMMPRIN expressions in gingival tissues. Immunohistochemistry was applied for CypA, EMMPRIN, MMP-1, MMP-2, MMP-9, as well as cell markers of macrophage, lymphocyte and neutrophil. CypA expression, alveolar bone loss, and inflammatory infiltrations were quantified followed by correlation analyses. RESULTS: Western blot revealed that CypA and EMMRPIN expressions were dramatically elevated in inflamed gingival tissues (ligature group) as compared to healthy gingival tissues (control group). The enhanced CypA and EMMPRIN expressions were highly consistent in cell localization on seriate sections. They were permanently co-localized in infiltrating macrophages and lymphocytes, as well as osteoclasts and osteoblasts in interradicular bone, but rarely expressed by infiltrating neutrophils. MMP-1, MMP-2, and MMP-9 expressions were also sharply increased in inflamed gingiva. MMP-2 and MMP-9 were mainly over-expressed by macrophages, while MMP-1 was over-produced by fibroblasts and infiltrating cells. The number of CypA-positive cells was strongly correlated with the ACJ-AC distance (r=0.839, p=0.000), the number of macrophages (r=0.972, p=0.000), and the number of lymphocytes (r=0.951, p=0.000). CONCLUSION: CypA is associated with the inflammatory infiltration and alveolar bone destruction of periodontitis. CypA-EMMPRIN interaction may exist in these pathological processes.
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Pérdida de Hueso Alveolar/enzimología , Basigina/metabolismo , Ciclofilina A/metabolismo , Periodontitis/enzimología , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/patología , Animales , Modelos Animales de Enfermedad , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Periodontitis/diagnóstico por imagen , Periodontitis/patología , Radiografía , Ratas , Ratas Sprague-DawleyRESUMEN
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
Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. In addition to the well-established catabolic effects (activation of bone resorption) of PTH, it is now recognized that intermittent PTH administration has anabolic effects (promotion of bone formation). As one of the commonest diseases, periodontitis cause the resorption of alveolar bone and finally result in the loss of teeth. So it is very pivotal step for periodontitis patients to inhibit the bone resorption and promote alveolar bone regeneration. In this review, we summarize the anabolic and catabolic effect on bone metabolism of PTH and its relative study in periodontal aspects. Moreover, we hypothesize that at the clinical level, the anabolic effect of PTH on bone metabolism may represent an attractive approach for stimulating bone formation, and thus improve the outcome of periodontal therapy.
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Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/fisiopatología , Modelos Biológicos , Hormona Paratiroidea/administración & dosificación , Periodontitis/tratamiento farmacológico , Periodontitis/fisiopatología , Pérdida de Hueso Alveolar/etiología , Animales , Humanos , Periodontitis/complicacionesRESUMEN
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).