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1.
Sensors (Basel) ; 21(1)2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33401750

RESUMO

In the hospital, a sleep postures monitoring system is usually adopted to transform sensing signals into sleep behaviors. However, a home-care sleep posture monitoring system needs to be user friendly. In this paper, we present iSleePost-a user-friendly home-care intelligent sleep posture monitoring system. We address the labor-intensive labeling issue of traditional machine learning approaches in the training phase. Our proposed mobile health (mHealth) system leverages the communications and computation capabilities of mobile phones for provisioning a continuous sleep posture monitoring service. Our experiments show that iSleePost can achieve up to 85 percent accuracy in recognizing sleep postures. More importantly, iSleePost demonstrates that an easy-to-wear wrist sensor can accurately quantify sleep postures after our designed training phase. It is our hope that the design concept of iSleePost can shed some lights on quantifying human sleep postures in the future.

2.
Ying Yong Sheng Tai Xue Bao ; 31(9): 3060-3066, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345507

RESUMO

Fertilization is an effective management to maintain and increase soil organic carbon (SOC) level in agroecosystems. Both microbial metabolism and plant component retention control SOC sequestration. Here, we used amino sugars and lignin as biomarkers to investigate the responses of distribution of microbial necromass and plant debris in a long-term cultivated soil (30 years) and SOC accumulation to different fertilization regime. The results showed that, compared with unfertilized treatment, inorganic fertilizer application (N fertilizer-only or the combination of organic or inorganic fertilizers) increased crop production and soil amino sugar accumulation, but did not affect the concentrations of lignin and SOC, indicating that inorganic fertilizer stimulated the assimilation of microbial substrate and accelerated the turnover of SOC and lignin in the plough layer. Compared with inorganic fertilizer treatment, long-term organic fertilizer application promoted SOC accumulation (38.3%), but did not affect amino sugar concentration in SOC, which indicated that soil could reach a 'saturation' state with respect to microbial residue accumulation. In contrast, the application of organic fertilizer increased the proportion of lignin in SOC,indicating that the contribution of plant residues to SOC persistence was enhanced. Compared with the manure-only treatment, organic-inorganic combined application mainly increased the contribution of amino sugar to SOC accumulation. Our findings indicated that long-term fertilization could affect SOC dynamics through modulating the accumulation processes of microbial necromass and plant debris.


Assuntos
Lignina , Solo , Agricultura , Carbono , Fertilização , Fertilizantes , Esterco , Microbiologia do Solo
3.
J Cell Mol Med ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33145962

RESUMO

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few studies have focused on the changes of NK, T- and B-cell subsets, inflammatory cytokines and virus-specific antibodies in patients with moderate COVID-19. A total of 11 RT-PCR-confirmed convalescent patients with COVID-19 and 11 patients with non-SARS-CoV-2 pneumonia (control patients) were enrolled in this study. NK, CD8+ T, CD4+ T, Tfh-like and B-cell subsets were analysed using flow cytometry. Cytokines and SARS-CoV-2-specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID-19 than in control patients (P = 0.017). Effector memory CD8+ T-cell counts significantly increased in patients with COVID-19 during a convalescent period of 1 week (P = 0.041). TIM-3+ Tfh-like cell and CD226+ Tfh-like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS+ Tfh-like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS-CoV-2. The increase in effector memory CD8+ T-cell counts, the up-regulation of inhibitory molecules and the down-regulation of active molecules on CD4+ T cells and Tfh-like cells in patients with COVID-19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID-19.

4.
World J Gastroenterol ; 26(30): 4501-4522, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32874061

RESUMO

BACKGROUND: No guideline recommends antiviral therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus (HBV) DNA viral load. AIM: To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection. METHODS: In total, 395 patients (30-65 years old) with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk. Endpoints to evaluate therapeutic efficacy included: (1) HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96; and (2) HBeAg clearance and seroconversion rates at weeks 48 and 96. RESULTS: HBV DNA levels ≤ 4 log10 IU/mL were 10.05% at week 48 and 18.59% at week 96 in the treatment group. The HBeAg clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96, respectively. However, HBV DNA levels ≤ 4 log10 IU/mL were 2.55% and 2.55% at weeks 48 and 96, respectively, and the HBeAg clearance rates were 3.06% and 5.61% at weeks 48 and 96, respectively, in the control group. The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance. CONCLUSION: High rates of HBV DNA reduction, HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments, and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase. The ability of the compound to modulate host immune function probably contributed to this effect.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32960770

RESUMO

Recently, the advances in passive brain-computer interfaces (BCIs) based on electroencephalogram (EEG) have shed light on real-world neuromonitoring technologies. However, human variability in the EEG activities hinders the development of practical applications of EEG-based BCI. To tackle this problem, many transfer-learning techniques perform supervised calibration. This kind of calibration approach requires task-relevant data, which is impractical in real-life scenarios such as drowsiness during driving. This study presents a transfer-learning framework for EEG decoding based on the low-dimensional representations of subjects learned from the pre-trial EEG. Tensor decomposition was applied to the pre-trial EEG of subjects to extract the underlying characteristics in subject, spatial and spectral domains. Then, the proposed framework assessed the characteristics to obtain the low-dimensional subject representations such that the subjects with similar brain dynamics can be identified. This method can leverage the existing data from other users and a small number of data from a rapid, non-task, unsupervised calibration from a new user to build an accurate BCI. Our results demonstrated that, in terms of prediction accuracy, the proposed low-dimensional subject representation-based transfer learning (LDSR-TL) framework outperformed the random selection and the Riemannian manifold approach in cognitive-state tracking, while requiring fewer training data. The results can greatly improve the practicability and usability of EEG-based BCI in the real world.

6.
Turk J Gastroenterol ; 31(6): 474-481, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32721919

RESUMO

BACKGROUND/AIMS: Intraoperative blood loss more than 400 mL during gastrointestinal surgery is an independent predictor of mortality. Desmopressin acetate (DDAVP) could reduce perioperative blood loss. Few studies have prompted concerning the effects of DDAVP on gastrointestinal surgery. This study was to investigate whether DDAVP can decrease blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery. MATERIALS AND METHODS: A multiple-centers, double-blind clinical trial was conducted, patients who underwent gastrointestinal surgery were recruited from 3 hospitals, randomly assigned to two different groups. Patients in the treatment group received desmopressin 0.3 ug/kg,30 min once a day after surgery, patients in the control group received 50 ml saline for 30 min. The primary outcome was the changes of hemoglobin at 24 hours after the surgery. And the secondary outcomes included coagulation function, urine volume, serum creatinine, and safety. RESULTS: There were 59 patients enrolled between 1 June 2015 and 1 June 2017. At 24hr.after surgery, a decrease in hemoglobin in the DDAVP group was significantly lower than that in the NS group (-5.0±6.9 g/L vs. -10.2±9.3g/L, p=0.03). Sonoclot® showed that the platelet function in the DDAVP group was higher than that in NS group at 24 hr. (2.56 ±0.59 vs. 1.91 ±0.72, p<0.05). There was no difference in urine volume and serum creatinine at 24 hr. between two group. CONCLUSION: DDAVP could reduce post-operation blood loss in patients with massive hemorrhage undergoing surgery by improving the platelet function. We observed no difference in urine volume and serum creatinine in two groups.

8.
Sci Rep ; 9(1): 6926, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31061448

RESUMO

The present study evaluated the growth response and sugar accumulation of lettuce exposed to different lighting modes of red and blue LED light based on the same daily light integral (7.49 µmol·m-2). Six lighting treatments were performed, that were monochromatic red light (R), monochromatic blue light (B), simultaneous red and blue light as the control (RB, R:B = 1:1), mixed modes of R, B and RB (R/RB/B, 4 h R to 4 h RB and then 4 h B), and alternating red and blue light with alternating intervals of 4 h and 1 h respectively recorded as R/B(4 h) and R/B(1 h). The Results showed that different irradiation modes led to obvious morphological changes in lettuce. Among all the treatments, the highest fresh and dry weight of lettuce shoot were both detected with R/B(1 h), significantly higher than the other treatments. Compared with plants treated with RB, the contents of fructose, glucose, crude fiber as well as the total sweetness index (TSI) of lettuce were significantly enhanced by R treatment; meanwhile, monochromatic R significantly promoted the activities of sucrose degrading enzymes such as acid invertase (AI) and neutral invertase (NI), while obviously reduced the activity of sucrose synthesizing enzyme (SPS). Additionally. The highest contents of sucrose and starch accompanied with the strongest activity of SPS were detected in plants treated with R/B(1 h). The alternating treatments R/B(4 h) and R/B(1 h) inhibited the activity of SS, while enhanced that of SPS compared with the other treatments, indicating that different light environment might influence sugar compositions via regulating the activities of sucrose metabolism enzymes. On the whole, R/B(1 h) was the optimal lighting strategy in terms of lettuce yield, taste and energy use efficiency in the present study.


Assuntos
Alface/fisiologia , Alface/efeitos da radiação , Luz , Açúcares/metabolismo , Biomassa , Metabolismo dos Carboidratos/efeitos da radiação , Fibras na Dieta , Regulação Enzimológica da Expressão Gênica , Redes e Vias Metabólicas , Fenótipo , Pigmentos Biológicos , Amido/metabolismo
9.
Ying Yong Sheng Tai Xue Bao ; 30(4): 1303-1311, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30994292

RESUMO

A field experiment was conducted to investigate the greenhouse gas emission at high latitude farmland in Northeast China. We monitored the greenhouse gas emission using the static chamber-gas chromatography method. Four nitrogen (N) fertilizers were used: conventional N fertilization (CN), slow release fertilizer (SLN), urea plus nitrification inhibitor and urease inhibitor (NIUI), and no nitrogen fertilizer (NN). The results showed that the yields under CN, SLN and NIUI treatments were 9618, 9376 and 9645 kg·hm-2, respectively. Compared with CN treatment, SLN increased soil N2O emission in the growing season and decreased N2O emission in the non-growing season. The cumulative N2O emission flux of NIUI treatment was 39.0% lower than that of CN. There were no significant differences in the annual cumulative CO2 emission flux among the treatments. The spring maize field in Northeast China was a weak CH4 sink. NIUI treatment promoted soil CH4 absorption in maize growing season compared with CN treatment. In summary, urea plus nitrification inhibitor and urease inhibitor could significantly reduce soil greenhouse gas emissions with high yield of maize.


Assuntos
Agricultura/métodos , Fertilizantes , Gases de Efeito Estufa/análise , Zea mays/crescimento & desenvolvimento , China , Metano/análise , Nitrogênio/análise , Óxido Nitroso/análise
10.
Oncogene ; 38(12): 2177-2191, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30459355

RESUMO

Poly (ADP-ribosylation), known as PARylation, is a post-translational modification catalyzed by poly (ADP-ribose) polymerases (PARP) and primarily removed by the enzyme poly (ADP-ribose) glycohydrolase (PARG). While the aberrant removal of post-translation modifications including phosphorylation and methylation has known tumorigenic effects, deregulation of PARylation has not been widely studied. Increased hydrolysis of PARylation chains facilitates cancer growth through enhancing estrogen receptor (ER)-driven proliferation, but oncogenic transformation has not been linked to increased PARG expression. In this study, we find that elevated PARG levels are associated with a poor prognosis in breast cancers, especially in HER2-positive and triple-negative subtypes. Using both in vitro and in vivo models, we demonstrate that heightened expression of catalytically active PARG facilitates cell transformation and invasion of normal mammary epithelial cells. Catalytically inactive PARG mutants did not recapitulate these phenotypes. Consistent with clinical data showing elevated PARG predicts poor outcomes in HER2+ patients, we observed that PARG acts in synergy with HER2 to promote neoplastic growth of immortalized mammary cells. In contrast, PARG depletion significantly impairs the growth and metastasis of triple-negative breast tumors. Mechanistically, we find that PARG interacts with SMAD2/3 and significantly decreases their PARylation in non-transformed cells, leading to enhanced expression of SMAD target genes. Further linking SMAD-mediated transcription to the oncogenicity of PARG, we show that PARG-mediated anchorage-independent growth and invasion are dependent, at least in part, on SMAD expression. Overall, our study underscores the oncogenic impact of aberrant protein PARylation and highlights the therapeutic potential of PARG inhibition in breast cancer.


Assuntos
Carcinogênese , Glicosídeo Hidrolases/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , DNA/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Glicosídeo Hidrolases/genética , Humanos , Camundongos , Metástase Neoplásica , Fenótipo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Análise de Sobrevida
11.
IEEE J Transl Eng Health Med ; 6: 2700410, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30245945

RESUMO

In this paper, the design of a smart headband for epileptic seizure detection is presented. The proposed headband consists of four key components: 1) an analog front-end circuitry; 2) an epileptic seizure detection tag (ESDT); 3) a Bluetooth low-power chip; and 4) customized electrodes. All the above components are integrated into a fabric headband with only 50.3 g. The smart headband system dissipates 55.89 mW. The epileptic seizure detection algorithm inside ESDT is validated by using Boston Children's Hospital's CHB-MIT scalp EEG clinical database with the detection rate of 92.68% and the false alarm of 0.527/h. We develop a service APP connected to the cloud so that the patients' health condition can be recorded and then referenced by doctors for further diagnosis or research.

12.
J Food Drug Anal ; 26(3): 973-984, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29976415

RESUMO

Obesity is associated with higher risks of developing diabetes and cardiovascular disease. Green tea, rich in polyphenolic compounds such as epigallocatechin gallate (EGCG) and epigallocatechin (EGC), has been shown to display anti-obesity effects. Houttuynia cordata leaves have also been shown to exhibit anti-obesity effects due to their chlorogenic acid content. Lactic acid bacteria are able to increase the production of polyphenolic compounds. This study aims to develop a novel anti-obesity fermentation product by combining H. cordata leaf tea with green tea, using Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) for fermentation due to the advantages of bioconverting the polyphenolic compounds. The regulation of adipogenesis factors and the anti-obesity effect of the NTU 101-fermented tea were evaluated in an in vitro 3T3-L1 pre-adipocyte model and an in vivo obese rat model, respectively. The results show that the NTU 101-fermented tea, which contained higher EGCG, EGC, and chlorogenic acid levels than unfermented tea, was able to inhibit the lipogenesis of mature 3T3-L1 adipocytes by the stimulation of lipolysis. Furthermore, the body weight gain, body fat pad, and feeding efficiency of obese rats, induced with a high fat diet, were decreased by the oral administration of NTU 101-fermented tea. The significant anti-obesity effect was probably due to lipolysis. However, NTU 101 bacteria cells and EGCG may also act as functional ingredients to contribute to the anti-obesity effects of NTU 101-fermented products.


Assuntos
Adipócitos/metabolismo , Fármacos Antiobesidade/metabolismo , Camellia sinensis/microbiologia , Houttuynia/microbiologia , Lactobacillus paracasei/metabolismo , Obesidade/dietoterapia , Preparações de Plantas/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Animais , Camellia sinensis/metabolismo , Diferenciação Celular , Fermentação , Houttuynia/metabolismo , Humanos , Lipogênese , Masculino , Camundongos , Obesidade/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Ratos , Ratos Sprague-Dawley
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(6): 899-903, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-32677401

RESUMO

OBJECTIVE: To identify key genes associated with hepatocellular carcinoma (HCC) through analyzing the functions of differentially expressed genes (DEGs) and the interactions of their encoded proteins. METHODS: The microarray dataset GSE45436 was downloaded from the Gene Expression Omnibus (GEO) database. The DEGs in hepatocellular carcinoma and adjacent tissues were analyzed using the R software. Bioinformatics tools DAVIA, STRING, GEPIA, Cytoscape, cBioPortal were applied to analyze the biological functions of the DEGs and their encoded protein interactions. RESULTS: A total of 375 DEGs were identified, consisting of 296 downregulated genes and 99 upregulated genes. The enriched functions and pathways of the DEGs included cell cycle, p53 signaling pathway, complement activation, and metabolism of xenobiotics by cytochrome P450. The PPIanalysis showed that TOP2A might be involved in the carcinogenesis of HCC. CONCLUSIONS: Differentially expressed genes in hepatocellular carcinoma and adjacent tissues and their encoded protein interactions revealed by the bioinformatics analysis provide guidance for further research on the molecular mechanism and targeted therapy of HCC. TOP2A may play a key role in HCC.

14.
J Immunol ; 198(7): 2578-2588, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28219887

RESUMO

Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell-derived autoantibody production. IL-21, a Tfh cell-derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus. We used blockade of IL-21 to dissect the mechanisms by which this cytokine promotes autoimmunity in murine lupus. Treatment of lupus-prone B6.Sle1.Yaa mice with an anti-IL-21 blocking Ab reduced titers of autoantibodies, delayed progression of glomerulonephritis and diminished renal-infiltrating Tfh and Th1 cells, and improved overall survival. Therapy inhibited excessive accumulation of Tfh cells coexpressing IL-21 and IFN-γ, and suppressed their production of the latter cytokine, albeit while not affecting their frequency. Anti-IL-21 treatment also led to a reduction in GC B cells, CD138hi plasmablasts, IFN-γ-dependent IgG2c production, and autoantibodies, indicating that Tfh cell-derived IL-21 is critical for pathological B cell cues in lupus. Normalization of GC responses was, in part, caused by uncoupling of Tfh-B cell interactions, as evidenced by reduced expression of CD40L on Tfh cells and reduced B cell proliferation in treated mice. Our work provides mechanistic insight into the contribution of IL-21 to the pathogenesis of murine lupus, while revealing the importance of T-B cellular cross-talk in mediating autoimmunity, demonstrating that its interruption impacts both cell types leading to disease amelioration.


Assuntos
Linfócitos B/imunologia , Interleucinas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Receptor Cross-Talk/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Autoimunidade/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , ELISPOT , Citometria de Fluxo , Masculino , Camundongos , Camundongos Mutantes
15.
IEEE Trans Image Process ; 26(5): 2246-2260, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28092551

RESUMO

In this paper, we propose a new framework for hierarchical image segmentation based on iterative contraction and merging. In the proposed framework, we treat the hierarchical image segmentation problem as a sequel of optimization problems, with each optimization process being realized by a contraction-and-merging process to identify and merge the most similar data pairs at the current resolution. At the beginning, we perform pixel-based contraction and merging to quickly combine image pixels into initial region-elements with visually indistinguishable intra-region color difference. After that, we iteratively perform region-based contraction and merging to group adjacent regions into larger ones to progressively form a segmentation dendrogram for hierarchical segmentation. Comparing with the state-of-the-art techniques, the proposed algorithm can not only produce high-quality segmentation results in a more efficient way, but also keep a lot of boundary details in the segmentation results.

16.
J Neurochem ; 140(3): 451-462, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27797401

RESUMO

During central nervous system development, oligodendrocyte progenitors elaborate multiple branched processes to contact axons and initiate myelination. Using cultured primary rat oligodendrocytes (OLGs), we have recently demonstrated that a cell surface protein belonging to the immunoglobulin superfamily, cell adhesion molecule-related, down-regulated by oncogenes (Cdon), is important in initiating OLG differentiation and axon myelination by promoting the formation of branched cellular processes; however, the molecular mechanism by which Cdon regulates OLG differentiation is not known. Here, using Cdon immunoprecipitation (IP) and liquid chromatography-tandem mass spectrometry analysis, we identified serine/threonine kinase TANK-binding kinase 1 (TBK1) as a candidate novel target of Cdon. We confirmed this interaction using co-IP and immunofluorescence with TBK1 antibodies, showing that TBK1 partly co-localizes with Cdon along cellular processes in puncta-like structures. We show that TBK1 is expressed throughout OLG differentiation, and surprisingly, that levels of phosphorylated TBK1 (ser172) increase during OLG maturation, while total levels of TBK1 protein decrease. To investigate function, TBK1 expression was knocked down using siRNA in OLG primary cultures, reducing protein levels by 69%. Two myelin-specific proteins, myelin basic protein and myelin-associated glycoprotein, were similarly reduced when examined at day 2 and day 4 of OLG differentiation. Reduced Cdon or TBK1 expression also decreased Akt phosphorylation at Threonine 308 in OLG. Our findings provide evidence that a Cdon-TBK1 complex is associated with Akt phosphorylation and early OLG differentiation.


Assuntos
Moléculas de Adesão Celular/metabolismo , Diferenciação Celular/fisiologia , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Moléculas de Adesão Celular/genética , Células Cultivadas , Feminino , Humanos , Masculino , Bainha de Mielina/genética , Ratos , Ratos Sprague-Dawley
17.
Neurochem Res ; 41(12): 3289-3299, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27639396

RESUMO

During development, the secreted molecule Sonic Hedgehog (Shh) is required for lineage specification and proliferation of oligodendrocyte progenitors (OLPs), which are the glia cells responsible for the myelination of axons in the central nervous system (CNS). Shh signaling has been implicated in controlling both the generation of oligodendrocytes (OLGs) during embryonic development and their production in adulthood. Although, some evidence points to a role of Shh signaling in OLG development, its involvement in OLG differentiation remains to be fully determined. The objective of this study was to assess whether Shh signaling is involved in OLG differentiation after neural stem cell commitment to the OLG lineage. To address these questions, we manipulated Shh signaling using cyclopamine, a potent inhibitor of Shh signaling activator Smoothened (Smo), alone or combined with the agonist SAG in OLG primary cultures and assessed expression of myelin-specific markers. We found that inactivation of Shh signaling caused a dose-dependent decrease in myelin basic protein (MBP) and myelin associated glycoprotein (MAG) in differentiating OLGs. Co-treatment of the cells with SAG reversed the inhibitory effect of cyclopamine on both myelin-specific protein levels and morphological changes associated with it. Further experiments are required to elucidate the molecular mechanism by which Shh signaling regulates OLG differentiation.


Assuntos
Proteínas Hedgehog/fisiologia , Células-Tronco Neurais/metabolismo , Oligodendroglia/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Diferenciação Celular , Células Cultivadas , Proteína Básica da Mielina/metabolismo , Glicoproteína Associada a Mielina/metabolismo , Células-Tronco Neurais/citologia , Oligodendroglia/citologia , Ratos Sprague-Dawley , Transdução de Sinais , Receptor Smoothened/antagonistas & inibidores , Receptor Smoothened/metabolismo , Alcaloides de Veratrum/farmacologia
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(2): 197-202, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27263294

RESUMO

OBJECTIVE: To investigate the prevention and therapeutic effects of Fuzheng Huayu Capsule on liver fibrosis in rats and its possible mechanism by regulating the expression of connective tissue growth factor (CTGF). METHODS: Forty Wistar rats were randomly divided into five groups: the normal group, the preventive group (the preventive experimental group and the preventive control group) and the treatment group (the treatment experimental group and the treatment control group). All the rats, except those in the normal group, were given CCl4 by subcutaneous injection and alcohol by oral adminstration to establish the model of liver fibrosis; meanwhile the rats in normal group were given same amount of olive oil by subcutaneous injection and water by oral administration. The preventive experimental group and control group were treated with Fuzheng Huayu crude drug 0.46 g/kg body mass through stomach irrigation and saline respectively once a day for four weeks during the modeling process. The treatment experimental group and control group were treated with Fuzheng Huayu crude drug 0.46 g/kg body mass through stomach irrigation and saline respectively once a day for four weeks after the modeling process. Blood was collected for the examination of liver function and serum fibrosis marker. HE staining was used to examine the pathological changes in liver tissue. The expression of CTGF was detected by immunohistochemistry. RESULTS: Compared with the preventive experimental group, total bilirubin (TB), alanine aminotransferase (ALT) and hyaluronic acid (HA) in the preventive control group decreased significantly (P < 0.05). Compared with the treatment control group, ALT and laminin (LN) in the treatment experimental group decreased significantly (P < 0.01). Compared with the treatment comtrol group, the inflammation and hepatic fibrosis in the treatment experimental group alleviated significantly. The expression of CTGF in the treatment experimental group were significantly lower than that in the treatment control group (P < 0.05). CONCLUSION: Fuzheng Huayu Capsule showed the prevention and therapeutic effects on experimental liver fibrosis. Meanwhile, Fuzheng Huayu Capsule could inhibit the CTGF expression in liver tissue, which may be one of the molecular mechanisms of these effects.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/tratamento farmacológico , Animais , Cápsulas , Fígado/metabolismo , Fígado/patologia , Ratos , Ratos Wistar
19.
J Neurosci ; 36(17): 4698-707, 2016 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-27122029

RESUMO

UNLABELLED: Multiple sclerosis (MS) lesions feature demyelination with limited remyelination. A distinct injury phenotype of MS lesions features dying back of oligodendrocyte (OL) terminal processes, a response that destabilizes myelin/axon interactions. This oligodendrogliopathy has been linked with local metabolic stress, similar to the penumbra of ischemic/hypoxic states. Here, we developed an in vitro oligodendrogliopathy model using human CNS-derived OLs and related this injury response to their distinct bioenergetic properties. We determined the energy utilization properties of adult human surgically derived OLs cultured under either optimal or metabolic stress conditions, deprivation of growth factors, and glucose and/or hypoxia using a Seahorse extracellular flux analyzer. Baseline studies were also performed on OL progenitor cells derived from the same tissue and postnatal rat-derived cells. Under basal conditions, adult human OLs were less metabolically active than their progenitors and both were less active than the rat cells. Human OLs and progenitors both used aerobic glycolysis for the majority of ATP production, a process that contributes to protein and lipid production necessary for myelin biosynthesis. Under stress conditions that induce significant process retraction with only marginal cell death, human OLs exhibited a significant reduction in overall energy utilization, particularly in glycolytic ATP production. The stress-induced reduction of glycolytic ATP production by the human OLs would exacerbate myelin process withdrawal while favoring cell survival, providing a potential basis for the oligodendrogliopathy observed in MS. The glycolytic pathway is a potential therapeutic target to promote myelin maintenance and enhance repair in MS. SIGNIFICANCE STATEMENT: The neurologic deficits that characterize multiple sclerosis (MS) reflect disruption of myelin (demyelination) within the CNS and failure of repair (remyelination). We define distinct energy utilization properties of human adult brain-derived oligodendrocytes and oligodendrocyte progenitor cells under conditions of metabolic stress that model the initial relapsing and subsequent progressive phases of MS. The observed changes in energy utilization affect both cell survival and myelination capacity. These processes may be amenable to therapeutic interventions to limit the extent of cumulative tissue injury and to promote repair in MS.


Assuntos
Doenças Desmielinizantes/patologia , Glicólise , Esclerose Múltipla/patologia , Oligodendroglia/metabolismo , Células-Tronco/metabolismo , Animais , Encéfalo/metabolismo , Morte Celular , Sobrevivência Celular , Células Cultivadas , Humanos , Bainha de Mielina/metabolismo , Oligodendroglia/patologia , Ratos , Ratos Sprague-Dawley
20.
Glia ; 64(6): 1021-33, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26988125

RESUMO

During central nervous system development, oligodendrocyte progenitors (OLPs) establish multiple branched processes and axonal contacts to initiate myelination. A complete understanding of the molecular signals implicated in cell surface interaction to initiate myelination/remyelination is currently lacking. The objective of our study was to assess whether Cdon, a cell surface protein that was shown to participate in muscle and neuron cell development, is involved in oligodendrocyte (OLG) differentiation and myelination. Here, we demonstrate that endogenous Cdon protein is expressed in OLPs, increasing in the early differentiation stages and decreasing in mature OLGs. Immunocytochemistry of endogenous Cdon showed localization on both OLG cell membranes and cellular processes exhibiting puncta- or varicosity-like structures. Cdon knockdown with siRNA decreased protein levels by 62% as well as two myelin-specific proteins, MBP and MAG. Conversely, overexpression of full-length rat Cdon increased myelin proteins in OLGs. The complexity of OLGs branching and contact point numbers with axons were also increased in Cdon overexpressing cells growing alone or in coculture with dorsal root ganglion neurons (DRGNs). Furthermore, myelination of DRGNs was decreased when OLPs were transfected with Cdon siRNA. Altogether, our results suggest that Cdon participates in OLG differentiation and myelination, most likely in the initial stages of development.


Assuntos
Moléculas de Adesão Celular/metabolismo , Diferenciação Celular/fisiologia , Bainha de Mielina/metabolismo , Oligodendroglia/citologia , Animais , Animais Recém-Nascidos , Axônios/metabolismo , Células Cultivadas , Gânglios Espinais/citologia , Camundongos , Proteína Básica da Mielina/metabolismo , Proteínas da Mielina/metabolismo , Neurogênese/fisiologia , Células-Tronco/citologia
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