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1.
Cell Commun Signal ; 17(1): 130, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639006

RESUMO

Following publication of the original article [1], the authors reported that the given name of Qinhao Wang was incorrectly published as Qinghao Wang. The original article has been corrected.

2.
In Vivo ; 33(6): 2169-2179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662553

RESUMO

BACKGROUND/AIM: The aim of this study was the development of a new osteoconductivity index to determine the bone healing capacities of bone substitute materials (BSM) on the basis of 3D microcomputed tomographic (µ-CT) data. MATERIALS AND METHODS: Sinus biopsies were used for the comparative analysis of the integration behavior of two xenogeneic BSM (cerabone® and Bio-Oss®). 3D µ-CT and data sets from histomorphometrical measurements based on 2D histological slices were used to measure the bone-material-contact and the tissue distribution within the biopsies. The tissue reactions to both BSM were microscopically analyzed. RESULTS: The 3D and 2D results of the osteoconductivity measurements showed comparable material-bone contacts for both BSM, but the 2D data were significantly lower. The same results were found when tissue distribution was measured in both groups. The histopathological analysis showed comparative tissue reactions in both BSM. CONCLUSION: Osteoconductivity index is a reliable measurement parameter for determining the healing capacities of BSM. The observed differences between both measurement methods could be assigned to the resolution capacity of µ-CT data that did not allow for a precise interface distinction between both BSM and bone tissue. Histomorphometrical data based on histological slides still allow for a more exact evaluation.

3.
ACS Appl Mater Interfaces ; 11(40): 36299-36306, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31514493

RESUMO

A dual-wavelength ratiometric electrochemiluminescence resonance energy transfer (ECL-RET) aptasensor based on the carbon nitride nanosheet (g-C3N4 NS) and metal-organic frameworks (Ru@MOFs) as energy donor-receptor pairs is first designed for the detection of the amyloid-ß (Aß) protein. The cathode ECL of g-C3N4 NS gradually decreased, whereas the anode ECL from Ru@MOF pyramidally enhanced along with the increasing concentration of Aß in a 0.1 M phosphate-buffered saline solution containing 0.1 M S2O82-. Additionally, it is worth noting that 2-amino terephthalic acid from MOF not only can load abundant amounts of luminophor Ru(bpy)32+ but also promote the conversion of more amounts of S2O82- that served as a coreactant accelerator into SO4•-, further enhancing the ECL signal of Ru@MOF. Besides, the ECL intensity from the g-C3N4 NS had a tremendous spectrum overlap with the UV-vis spectrum of Ru@MOF, demonstrating the high-efficiency ECL-RET from g-C3N4 NS to Ru@MOF. According to the ratio of ECL460nm/ECL620nm, the constructed aptasensor for the detection of Aß showed a wide linear range from 10-5 to 500 ng/mL and a low detection limit of 3.9 fg/mL (S/N = 3) with a correction coefficient of 0.9965. The obtained results certified that the dual-wavelength ratiometric ECL sensor could provide a reliable direction and have the potential for application in biosensing and clinical diagnosis fields.

4.
Food Funct ; 10(9): 5768-5778, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31454000

RESUMO

In this study, we aimed at investigating the antiinflammatory activity of the freeze-dried fruit powder of Actinidia arguta (FAA) on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice and the effect of its extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. For pharmacodynamic studies, the oral administration of FAA (300 or 600 mg kg-1) could decrease the disease activity index (DAI), reduce the incidence of colon and spleen edemas (caused by inflammation), and alleviate the pathological changes in UC. For research involving biochemical indicators, FAA could decrease the expression of inflammatory markers (such as myeloperoxidase (MPO)) and attenuate the oxidative stress levels. ELISA results revealed that the expressions of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) were downregulated by FAA. Furthermore, the expression levels of the inflammation-induced activation of p38, JNK, and ERK were decreased by FAA. Hence, it was concluded that FAA could alleviate the UC symptoms in mice and the inflammatory response of macrophages via the MAPK signal pathway. Overall, FAA might have the potential to treat UC when used as a dietary supplement.

5.
Yi Chuan ; 41(6): 524-533, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31257200

RESUMO

Normal development of the cerebral cortex is a basis for the formation and function of mammalian brains. During this process, the radial migration of cortical neurons, as well as the axon projection into specific layers, are the most important steps regulated by some transcription factors, but the underlying molecular mechanisms are still obscure. BMAL1 (brain and muscle Arnt-like protein 1) is a newly identified transcription factor that plays important roles in the circadian rhythms. It was recently found to regulate the proliferation of hippocampal neuronal progenitor/precursor cells (NPCs), implicating Bmal1 in the brain development. Here we employed both RT-RCR and real-time PCR to explore the expression pattern of the Bmal1 gene in the developing brain. We found BMAl1 is enriched in the brain cortex during the perinatal stages and peaked in P3 mouse brains. Combined with in utero electroporation and interference with RNAi, we found that reducing the expression level of Bmal1 in neurons, the radial migration of embryonic cortical neurons was largely delayed, in a gene dose-effect pattern. Moreover, reducing the level of Bmal1 expression in mouse brains, the axonal projection in the corpus callosum was also disrupted from ipsilateral to the lateral cerebral hemisphere. These findings indicate that BMAL1 is essential for the radial migration of neurons in the cerebral cortex and the axonal projection of the corpus callosum, providing insights into the molecular mechanisms of cerebral cortex development.


Assuntos
Fatores de Transcrição ARNTL/fisiologia , Axônios , Movimento Celular , Córtex Cerebral/embriologia , Neurogênese , Animais , Feminino , Camundongos , Gravidez
6.
Mol Med Rep ; 20(2): 1893-1900, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257503

RESUMO

Mutations of isocitrate dehydrogenase (IDH) 1 and 2 occur in low­grade gliomas, acute myeloid leukemias and other types of solid cancer. By catalyzing the reversible conversion between isocitrate and α­ketoglutarate (α­KG), IDH1 and 2 contribute to the central process of metabolism, including oxidative and reductive metabolism. IDH1 and 2 mutations result in the loss of normal catalytic function and acquire neomorphic activity, facilitating the conversion of α­KG into an oncometabolite, (R)­2­hydroxyglutarate, which can cause epigenetic modifications and tumorigenesis. Small­molecule inhibitors of mutant IDH1 and 2 have been developed, and ongoing clinical trials have shown promising results in hematological malignancies, but not in gliomas. These previous findings make it necessary to identify the mechanism and develop more effective therapies for IDH1­mutant gliomas. In the present study, it was demonstrated that under hypoxic conditions, patient­derived primary glioma cells and HCT116 cells, both of which carry a monoallelic IDH1 arginine 132 to histidine mutation (R132H), have a slower growth rate than the corresponding wild­type IDH1 cells. Western blot analysis showed that IDH1 R132H­mutant cancer cells exhibited upregulated IDH2 protein expression under hypoxic conditions. Furthermore, the silencing of IDH2 using small interfering RNA significantly inhibited the growth of IDH1­mutant cells under hypoxic conditions. Finally, [U­13C5]glutamine tracer analysis showed that IDH2 knockdown reduced the reductive carboxylation of α­KG into isocitrate in HCT116R132H/+ cells under hypoxic conditions. The present study showed for the first time, to the best of our knowledge, that IDH2 plays a compensatory role in maintaining reductive carboxylation­dependent lipogenesis and proliferation in IDH1 R132H tumor cells. Therefore, IDH2 could serve as a potential anti­tumor target for IDH1­mutant tumors, which may provide a new strategy for treatment.

7.
Sensors (Basel) ; 19(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146350

RESUMO

Monitoring plant nitrogen (N) in a timely way and accurately is critical for precision fertilization. The imaging technology based on visible light is relatively inexpensive and ubiquitous, and open-source analysis tools have proliferated. In this study, texture- and geometry-related phenotyping combined with color properties were investigated for their potential use in evaluating N in pakchoi (Brassica campestris ssp. chinensis L.). Potted pakchoi treated with four levels of N were cultivated in a greenhouse. Their top-view images were acquired using a camera at six growth stages. The corresponding plant N concentration was determined destructively. The quantitative relationships between the nitrogen nutrition index (NNI) and the image-based phenotyping features were established using the following algorithms: random forest (RF), support vector regression (SVR), and neural network (NN). The results showed the full model based on the color, texture, and geometry-related features outperforms the model based on only the color-related feature in predicting the NNI. The RF full model exhibited the most robust performance in both the seedling and harvest stages, reaching prediction accuracies of 0.823 and 0.943, respectively. The high prediction accuracy of the model allows for a low-cost, non-destructive monitoring of N in the field of precision crop management.

8.
J Zhejiang Univ Sci B ; 20(7): 598-604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168973

RESUMO

There are differences in individual cardiovascular responses to the administration of dexmedetomidine, a highly selective α2A-adrenergic receptor (ADRA2A) agonist. The aim of this study was to investigate ADRA2A gene polymorphisms in the Chinese Han population and their association with the cardiovascular response to intravenous dexmedetomidine infusion. Sixty elective surgery patients of Chinese Han nationality were administered 1 µg/kg dexmedetomidine intravenously over 10 min as a premedication. ADRA2A C-1291G and A1780G polymorphism status was determined in these patients, and their relationships to changes in blood pressure and heart rate after dexmedetomidine administration were analyzed. There were neither significant differences in systolic or diastolic blood pressure changes in individuals with different A1780G and C-1291G genotypes after dexmedetomidine administration, nor in heart rates among the different A1780G genotypes. However, there were significant differences in changes in heart rates in patients with different C-1291G genotypes. There were no significant differences in the sedative effects of dexmedetomidine among different A1780G and C-1291G genotypes. Logistic regression revealed that the C-1291G polymorphism was associated with differential decreases in heart rate after intravenous infusion of dexmedetomidine. These findings indicate that the ADRA2A C-1291G polymorphism can affect heart rate changes in patients after intravenous infusion of dexmedetomidine.

9.
Cell Commun Signal ; 17(1): 44, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092266

RESUMO

BACKGROUND: Over-activation of phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is one of important mechanisms to promote castration resistant prostate cancer, the final stage of prostate cancer (PCa). Dysregulation of PP1-meditaed AKT dephosphorylation might contribute to such an event but is not fully understood. As a newly identified tumor suppressor, MIIP exerts its role in various types of cancer but has not been investigated in PCa. RESULTS: We first demonstrated that overexpression of migration and invasion inhibitory protein (MIIP) in human PCa cell lines suppresses their growth while knockdown of MIIP does the opposite in vitro. Although MIIP has no effect on the expression of AR and its target genes or the nuclear translocation of AR in AR-positive PCa cells, MIIP overexpression significantly inhibits activation of AKT-mTOR pathway in both AR- positive and negative PCa cells whereas knockdown of MIIP enhances AKT-mTOR signaling. Using Western blot, immunofluorescence co-localization and co-immunoprecipitation analysis, we found that MIIP interacts with PP1α via its C-terminal part but does not affect its protein level. Importantly, silence of PP1α reversed the inhibitory effect of MIIP on AKT phosphorylation and cell growth in PCa cell lines, while MIIP∆C, which is incapable of interacting with PP1α, loses MIIP's effect, suggesting that MIIP exerts its roles via interaction with PP1α. Further, MIIP overexpression inhibits the growth of both AR- positive and negative PCa xenograft in nude mice. Finally, immunohistochemical staining of PCa tissue microarray showed that MIIP expression level is downregulated in PCa and negatively correlated with Gleason score of PCa. CONCLUSION: We discovered that MIIP is a novel suppressor of oncogenic AKT-mTOR signaling in PCa by facilitating PP1-meditaed AKT dephosphorylation. Our study further emphasized the tumor suppressive role of MIIP and illustrated a novel mechanism.

10.
Nat Commun ; 10(1): 1516, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944337

RESUMO

Large-scale metabolite annotation is a challenge in liquid chromatogram-mass spectrometry (LC-MS)-based untargeted metabolomics. Here, we develop a metabolic reaction network (MRN)-based recursive algorithm (MetDNA) that expands metabolite annotations without the need for a comprehensive standard spectral library. MetDNA is based on the rationale that seed metabolites and their reaction-paired neighbors tend to share structural similarities resulting in similar MS2 spectra. MetDNA characterizes initial seed metabolites using a small library of MS2 spectra, and utilizes their experimental MS2 spectra as surrogate spectra to annotate their reaction-paired neighbor metabolites, which subsequently serve as the basis for recursive analysis. Using different LC-MS platforms, data acquisition methods, and biological samples, we showcase the utility and versatility of MetDNA and demonstrate that about 2000 metabolites can cumulatively be annotated from one experiment. Our results demonstrate that MetDNA substantially expands metabolite annotation, enabling quantitative assessment of metabolic pathways and facilitating integrative multi-omics analysis.


Assuntos
Redes e Vias Metabólicas , Metabolômica/métodos , Modelos Biológicos , Algoritmos , Animais , Cromatografia Líquida/métodos , Bases de Dados Factuais , Drosophila/metabolismo , Regulação da Expressão Gênica , Gluconeogênese , Metaboloma , Metabolômica/instrumentação , Espectrometria de Massas em Tandem/métodos , Transcriptoma
11.
Biosens Bioelectron ; 132: 203-209, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30875632

RESUMO

A stable sandwiched electrochemiluminescence (ECL) aptasensor was originally constructed established upon Ru(bpy)32+-doped silica nanoparticles (RuSiO2 NPs) with ferrocene carboxylic acid-aptamer (Fc-aptamer) to quantitatively detect cytochrome c (Cyt C). Herein, RuSiO2 NPs and Fc-aptamer were respectively prepared through the microemulsion method and amide reaction to fabricate the ECL aptasensor. Furthermore, Fc-aptamer was used as quenching probe for quenching the ECL emission of RuSiO2 NPs. In detail, RuSiO2 NPs were primarily immobilized onto the electrodes by the film-forming function of chitosan. Subsequently, the aptamer was incubated onto the decorated GCE via crosslinking with glutaraldehyde (GA). After Cyt C was connected to the GCE via immunoreaction, Fc-aptamer was immobilized onto the modified electrodes owing to the specific recognition between antigens and aptamer. Ultimately, ECL signals markedly descended owing to the poor electricity conductivity of proteins and superior quenching effect of Fc-aptamer. Under optimum conditions, the designed ECL aptasensor indicated an accurate analysis for Cyt C in a rang of 0.001-100 nM with a detection limit of 0.48 pM (S/N = 3).


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Citocromos c/sangue , Compostos Ferrosos/química , Metalocenos/química , Nanopartículas/química , Rutênio/química , Dióxido de Silício/química , Citocromos c/análise , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Medições Luminescentes/métodos
12.
J Chem Inf Model ; 59(5): 2309-2323, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30801189

RESUMO

Cassane diterpenoids (CAs), recognized as main constituents of many medical plants of the genus Caesalpinia, exhibit diverse bioactivities, including anti-inflammatory and immunomodulatory activity, and also showed a therapeutic effect on rheumatoid arthritis (RA) according to previous work, including ours. In this study, 102 CA compounds were selected to explore the possible molecular mechanism of this class of natural products on anti-inflammatory and immunomodulatory activity using RA as a disease model through a series of in silico methods: chemical-similarity-based target prediction, molecular docking, and molecular dynamics (MD) simulation. As a consequence, four signaling pathways (TCR signaling pathway, TLR signaling pathway, VEGF signaling pathway, and osteoclast differentiation pathway) by which CAs exert their effect on inflammation and immunomodulation were identified. Furthermore, the binding modes of CAs complexing with several crucial targets, which were picked out by credible docking results and took part in these signaling pathways, were explored by MD simulations. This is the first time that the molecular mechanism of the anti-RA activity of natural CAs has been investigated with in silico methods, and these findings might explain the activity of CAs on anti-inflammation and immunomodulation, which could supply a valuable reference for drug design research on CAs.

13.
Neuroimmunomodulation ; 26(2): 102-110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30783039

RESUMO

OBJECTIVES: Inflammation and apoptosis play a critical role in the pathological progress of traumatic brain injury (TBI). Isoliquiritigenin is a bioactive component extracted from licorice roots, which possesses anti-inflammatory and anti-apoptotic properties. This study aims to investigate the potential effects of isoliquiritigenin on neuroinflammation in a rat model of TBI. METHODS: The SH-SY5Y cells were subjected to cell injury induced by shear stress and the effect of isoliquiritigenin on cell apoptosis was measured. Male rats received a controlled cortical impact to induce TBI and were then treated with isoliquiritigenin (20 mg/kg). Brain edema and contusion volume were measured to assess brain damage. Morris water maze, the beam-balance test, and the beam-walk test were performed to evaluate the cognitive and motor functions. RESULTS: Levels of proinflammatory cytokines and apoptotic regulators were measured. Results showed that isoliquiritigenin reduced shear stress-induced cell apoptosis in vitro. In young rats subjected to TBI, treatment of isoliquiritigenin reduced brain damage and attenuated motor and cognitive impairments. Isoliquiritigenin also reduced the level of proinflammatory cytokines and Bax and increased Bcl-2 and Bcl-xL in TBI rats. CONCLUSIONS: These findings suggest that isoliquiritigenin possesses beneficial effects in TBI by inhibiting inflammation and apoptosis.

14.
Mol Biol Rep ; 46(2): 1577-1584, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30689186

RESUMO

Pure breed dogs of Western origin are increasingly more popular in China as is a need to differentiate breeds and individual dogs for personal and forensic reasons. Research on genetic diversities of the canine population in China is rarely conducted. In this study, genetic distributions and forensic efficiencies of 19 canine STR loci in Labrador Retriever population from China were evaluated by using one available commercial canine kit in China. This panel was used to genetically define 214 Labrador Retrievers in China, as an example of one of the most important Western breeds and to compare them with Labrador Retrievers from America based on three overlapping STR loci. Moreover, genetic relationship analyses between Labrador Retriever population and two reference populations in America were performed. All 19 STR loci were polymorphic and conformed to Hardy-Weinberg equilibrium in the studied population. The STR panel was able to discern individual dogs with a high degree of accuracy. Breed-wide genetic heterozygosity comparisons based on present and published allele frequencies revealed that the studied population had the lower genetic heterozygosity than canine populations in America. Principal component analysis among Labrador Retriever population and other reference populations showed that the studied Labrador Retrievers were genetically close to the retriever breeds in America. Population genetic structure analyses among these canine breeds further revealed genetic differentiations between the studied Labrador Retriever population and other compared breeds. In conclusion, these STR loci had relatively high forensic values in Labrador Retriever population in China, which could be employed for individual identification and kinship testing.


Assuntos
Cães/genética , Seleção Artificial/genética , Alelos , Animais , Cruzamento/métodos , China , Impressões Digitais de DNA/métodos , Genética Forense/métodos , Frequência do Gene/genética , Genética Populacional/métodos , Heterozigoto , Repetições de Microssatélites , Polimorfismo Genético , Estados Unidos
15.
Hepatology ; 70(1): 84-97, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30653687

RESUMO

Mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is an integral component of the respiratory chain, and recent studies have suggested that it plays an important role in hepatic glucose homeostasis. However, its function in hepatic lipid metabolism is unclear. Here, we identified a role for mGPDH in nonalcoholic fatty liver disease (NAFLD). Specifically, mGPDH expression and activity were lower in fatty livers from patients and mice with NAFLD (ob/ob, high-fat diet [HFD] and db/db). Liver-specific depletion of mGPDH in mice or mGPDH knockdown in cultured hepatocytes exacerbated diet-induced triglyceride accumulation and steatosis through enhanced lipogenesis. RNA-sequencing revealed that mGPDH regulated endoplasmic reticulum (ER)-related proteins and processes. mGPDH deletion exacerbated tunicamycin (ER stress inducer)-induced hepatic steatosis, whereas tauroursodeoxycholic acid (ER stress inhibitor) rescued mGPDH depletion-induced steatosis on an HFD. Moreover, ER stress induced by mGPDH depletion could be abrogated by the intracellular Ca2+ chelator 1,2-bis (2-aminophenoxy) ethane N,N,N´,N´-tetraacetic acid acetoxymethyl ester, mitochondrial permeability transition pore (mPTP) inhibitor cyclosporine A, or cyclophilin-D (Cyp-D) knockdown. mGPDH promoting Cyp-D ubiquitination was also observed. Finally, liver-specific mGPDH overexpression attenuated hepatic steatosis in ob/ob and HFD mice. Conclusion: mGPDH is a pivotal regulator of hepatic lipid metabolism. Its deficiency induces ER stress by suppressing Cyp-D ubiquitination, a key regulator of the mitochondrial Ca2+ conductance channel mPTP, and results in hepatic steatosis. mGPDH may be a potential therapeutic target for the treatment of NAFLD.

16.
Int J Legal Med ; 133(3): 689-697, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30604102

RESUMO

Capillary electrophoresis (CE) is widely used in forensic genetics to study short tandem repeats (STRs). Recently, next-generation sequencing (NGS) platforms have facilitated the development of new strategies for forensic DNA typing. Several studies have shown that NGS successfully analyzes challenging samples. However, because NGS is complicated and time-consuming, it remains unclear whether NGS platforms offer significant advantages over CE for all forensic cases. Here, the MiSeq FGx system was used to test some cases that had previously been analyzed using CE. These cases included paternity test cases in which some samples exhibited locus inconsistencies; samples with off-ladder (OL) alleles; samples with triallelic patterns; and samples with amelogenin test abnormalities. The results generated by MiSeq FGx were compared to those previously generated by CE. The MiSeq FGx and CE results were consistent with the exception of three samples, where inconsistencies were observed at the Penta D locus. For all three incongruent samples, the MiSeq FGx results were correct. Sequence analysis indicated that, in two cases, mismatches were due to undetected alleles rather than mutations. In two additional cases, mutation sources were identified, and in a fifth case, mutation step size was reconsidered. MiSeq FGx was used to identify OL alleles and samples with amelogenin test abnormalities. For cases where verification was required via CE analysis, the simultaneous NGS amplification of several types of multiple genetic markers improved testing efficiency. In addition, we identified additional sequence variants at autosomal, Y chromosomal, and X chromosomal STR loci in the Han Chinese population from northern China. Our results will be useful for future forensic analyses of STR genotypes in Chinese populations. It is likely that NGS would be more widely used in forensic genetics if costs and procedure complexity were reduced.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Análise de Sequência de DNA , China , Cromossomos Humanos X , Cromossomos Humanos Y , Impressões Digitais de DNA , Eletroforese Capilar , Grupos Étnicos/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Mutação , Reação em Cadeia da Polimerase
17.
Neurochem Res ; 44(4): 849-858, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30635843

RESUMO

Lack of blood or glucose supply is the most common pathological factor in the brain. To cope with such an energy stress, initiating programmed autophagic processes in neurons is required. However, the mechanisms controlling neuronal autophagy during starvation remain far from clear. Here, we report an essential role of 14-3-3γ in starvation-activated neuronal autophagic influx signaling and elucidate the underlying mechanism. Double-fluorescent immunostaining demonstrates that 14-3-3γ protein elevation is well co-localized with Beclin-1 and LC3 elevation in cortical neurons in ischemic brains. Starvation treatment activates autophagic influx and upregulates Beclin-1 and only the γ isoform of 14-3-3 in N2a cells and cultured cortical neurons. Suppressing overall 14-3-3 function by difopein overexpression or knocking-out the γ isoform of 14-3-3 is sufficient to abolish starvation-induced Beclin-1 induction and LC3 activation while overexpressing 14-3-3γ but no other 14-3-3 isoform significantly upregulate Beclin-1-LC3 signaling. Upon starvation, 14-3-3γ binds more p-ß-catenin but less Beclin-1. Finally, overexpressing 14-3-3γ reactivates ß-catenin-suppressed Beclin-1-LC3 signaling in neuronal cells. Taken together, our data reveal that starvation-induced 14-3-3γ is required for ß-catenin-Beclin-1-LC3-autophagy in starved neurons in vitro and in vivo, which may provide insights in the treatment of neurologic diseases such as stoke.


Assuntos
Proteínas 14-3-3/biossíntese , Autofagia/fisiologia , Proteína Beclina-1/biossíntese , Proteínas Associadas aos Microtúbulos/biossíntese , Neurônios/metabolismo , beta Catenina/biossíntese , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/patologia , Regulação para Cima/fisiologia
18.
Brain Topogr ; 32(2): 240-254, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30599076

RESUMO

To provide optional force and speed control parameters for brain-computer interfaces (BCIs), an effective feature extraction method of imagined force and speed of hand clenching based on electroencephalography (EEG) was explored. Twenty subjects were recruited to participate in the experiment. They were instructed to perform three different actual/imagined hand clenching force tasks (4 kg, 10 kg, and 16 kg) and three different hand clenching speed tasks (0.5 Hz, 1 Hz, and 2 Hz). Topographical maps parameters and brain network parameters of EEG were calculated as new features of imagined force and speed of hand clenching, which were classified by three classifiers: linear discrimination analysis, extreme learning machines and support vector machines. Topographical maps parameters were better for recognition of the hand clenching force task, while brain network parameters were better for recognition of the hand clenching speed task. After a combination of five types of features (energy, power spectrum of the autoregressive model, wavelet packet coefficients, topographical maps parameters and brain network parameters), the recognition rate of the hand clenching force task was 97%, and that of the hand clenching speed task was as high as 100%. The brain topographical and the brain network parameters are expected to improve the accuracy of decoding the EEG signal of imagined force and speed of hand clenching. A more efficient brain network may facilitate the recognition of force/speed of hand clenching. Combined features could significantly improve the single-trial recognition rate of imagined forces and speeds of hand clenching. The current study provides a new idea for the imagined force and speed of hand clenching that offers more control intention instructions for BCIs.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Mãos/fisiologia , Rede Nervosa/fisiologia , Adulto , Encéfalo/anatomia & histologia , Eletroencefalografia/métodos , Eletromiografia , Feminino , Humanos , Imaginação , Cinética , Aprendizado de Máquina , Masculino , Contração Muscular/fisiologia , Recognição (Psicologia) , Máquina de Vetores de Suporte , Adulto Jovem
19.
Biosens Bioelectron ; 124-125: 59-65, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30343157

RESUMO

An electrochemiluminescence (ECL) analytical platform was initially proposed based on the electrochemiluminescence resonance energy transfer (ECL-RET) mechanism for ultrasensitive detection of Concanavalin A (Con A). In this protocol, the glucose functionalized carboxylic g-C3N4 nanosheets (g-C3N4-COOH@Glu) and MnO2 nanoparticles covered carboxylic multi-wall carbon nanotubes (BSA@MnO2-MWCNTs-COOH@Glu) were synthesized and acted as ECL-RET electron donor and acceptor, respectively. Herein, glucose was served as the recognition element for binding Con A and MWCNTs was utilized as the carrier materials for loading MnO2. When the quenching probe BSA@MnO2-MWCNTs-COOH@Glu was incubated onto the modified electrodes via the specific carbohydrate-Con A interaction, the ECL signals of g-C3N4-COOH@Glu which used S2O82- as its coreactant have drastically declined. Under optimum conditions, this biosensor performed a sensitive detection of the Con A ranging from 1 × 10-5 to 1 × 104 ng/mL with a detection limit of 2.2 fg/mL (S/N = 3). Moreover, favorable analytical outcomes for detecion Con A in actual serum samples were obtained, exhibiting huge applications in clinical diagnosis of this assay.


Assuntos
Técnicas Biossensoriais/métodos , Concanavalina A/isolamento & purificação , Técnicas Eletroquímicas/métodos , Nanopartículas/química , Concanavalina A/química , Transferência de Energia , Hipersensibilidade , Limite de Detecção , Medições Luminescentes , Compostos de Manganês/química , Nanotubos de Carbono/química
20.
Hum Pathol ; 2018 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-30584892

RESUMO

Primary cytomegalovirus (CMV) infection is rare in immunocompetent hosts and generally asymptomatic. CMV infective gastritis in patients without immunosuppression is very unusual. A 44-year-old man presented with complaints of intermittent epigastric pain. He had no history of organ transplantation, human immunodeficiency virus infection, or immunosuppression of any type. Upper gastrointestinal endoscopy revealed ulcers in the gastric antrum and uplift of the gastric body. Computed tomography scan showed obvious thickening of the gastric wall and enlargement of retroperitoneal lymph nodes, suggesting malignancy. However, the first biopsy only showed ulcerative inflammation, necrosis, and mucosal erosions around the ulcer. Repeat biopsy and histopathological examination showed CMV inclusions in glandular endothelial cells. Immunohistochemistry findings supported the diagnosis of CMV infective gastritis. Symptoms subsided after treatment with intravenous ganciclovir, and the gastric ulceration and surrounding mucosal inflammation decreased. This case report and review of literature is presented to increase awareness regarding this rare disease.

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