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1.
Artigo em Inglês | MEDLINE | ID: mdl-32124022

RESUMO

Codeine-containing cough syrup (CCS) is considered as one of the most popular drug of dependence among adolescents because of its inexpensiveness and easy availability. However, its relationship with neurobiological effects remains sparsely explored. Herein, we examined how high-impulse behaviours relate to changes in the brain structural networks. Forty codeine-containing cough syrup dependent (CCSD) users and age-, gender-, and number of cigarettes smoked per day -matched forty healthy control (HC) subjects underwent structural brain imaging via MRI. High-impulse behaviour was assessed using the 30-item self-rated Barratt Impulsiveness Scale (BIS-11), and structural networks were constructed using diffusion tensor imaging and AAL-90 template. Between-group topological metrics were compared using nonparametric permutations. Benjamin-Hochberg false discovery rate correction was used to correct for multiple comparisons (P < 0.05). The relationships between abnormal network metrics and clinical characteristics of CCS dependent (BIS-11 total score, CCS- dependent duration and mean dose) were examined by Spearman's correlation. Structural networks of the CCSD group demonstrated lower small-world properties than those of the HC group. Abnormal changes in nodal properties among CCSD users were located mainly in the frontal gyrus, inferior parietal lobe and olfactory cortex. NBS analysis further indicated disrupted structural connections between the frontal gyrus and multiple brain regions. There were significant correlations between abnormal nodal properties of the frontal gyrus and clinical characteristics (BIS-11 total score, CCS dependent duration and mean dose) in the CCSD group. These findings suggest that the high-impulse behavioural expression in CCS addiction is associated with widespread brain regions, particularly within those in the frontal cortex. Aberrant brain regions and disrupted connectivity of structural network may be the bases of neuropathology for underlying symptoms of high-impulse behaviours in CCSD users, which may provide a novel sight to better treat and prevent codeine dependency in adolescents.

2.
Neuroimage Clin ; 25: 102175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31954985

RESUMO

Patients with hepatitis B virus (HBV)-related cirrhosis (HBV-RC) and minimal hepatic encephalopathy (MHE) exhibit alterations in homotopic inter-hemispheric functional connectivity (FC) and corpus callosum (CC) degeneration. However, the progression of inter-hemispheric dysconnectivity in cirrhotic patients from no MHE (NMHE) to MHE and its association with the progression of diseased-related cognitive impairment remain uncharacterized. We hypothesized that inter-hemispheric dysconnectivity exists in NMHE patients and further deteriorates at the MHE stage, which is associated with performance measured by psychometric hepatic encephalopathy scores (PHES) that can characterize cirrhotic patients with NMHE and MHE. Using inter-hemispheric homotopic FC and CC (and its subfields) volumetric measurements in 31 patients with HBV-RC (17 with NMHE and 14 with MHE) and 37 healthy controls, we verified that MHE patients had significant attenuated inter-hemispheric homotopic FC in the bilateral cuneus, post-central gyrus, inferior parietal lobule, and superior temporal gyms, as well as CC degeneration in total CC, CC2, CC3, and CC4 (each comparison had a corrected P < 0.05). In contrast, NMHE patients had relatively less severe inter-hemispheric homotopic FC and no CC degeneration. In addition, the degeneration of the CC and inter-hemispheric homotopic functional disconnections correlated with poor PHES performances in all cirrhotic patients (NMHE and MHE). Furthermore, impairment of inter-hemispheric homotopic FC partially mediated the association between CC degeneration and worse PHES performance. Notably, a combination of inter-hemispheric homotopic FC and CC volumes had higher discriminative values according to the area under the curve (AUC) score (AUC = 0.908, P < 0.001) to classify patients into MHE or NMHE groups when compared with either alone. Our findings shed light on the progression of inter-hemispheric dysconnectivity in relation to the progression of disease-related cognitive impairment in patients with HBV-RC.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31996651

RESUMO

PURPOSE: To determine the predictive features of thymic carcinomas and high-risk thymomas using random forest algorithm. METHODS: A total of 137 patients with pathologically confirmed high-risk thymomas and thymic carcinomas were enrolled in this study. Three clinical features and 20 computed tomography features were reviewed. The association between computed tomography features and pathological patterns was analyzed by univariate analysis and random forest. The predictive efficiency of the random forest algorithm was evaluated by receiver operating characteristic curve analysis. RESULTS: There were 92 thymic carcinomas and 45 high-risk thymomas in this study. In univariate analysis, patient age, presence of myasthenia gravis, lesion shape, enhancement pattern, presence of necrosis or cystic change, mediastinal invasion, vessel invasion, lymphadenopathy, pericardial effusion, and distant organ metastasis were found to be statistically different between high-risk thymomas and thymic carcinomas (all P < 0.01). Random forest suggested that tumor shape, lymphadenopathy, and the presence of pericardial effusion were the key features in tumor differentiation. The predictive accuracy for the test data and whole data was 94.73% and 96.35%, respectively. Further receiver operating characteristic curve analysis showed the area under the curve was 0.957 (95% confidence interval, 0.986-0.929). CONCLUSIONS: The random forest model in the present study has high efficiency in predictive diagnosis of thymic carcinomas and high-risk thymomas. Tumor shape, lymphadenopathy, and pericardial effusion are the key features for tumor differentiation. Thymic tumors with irregular shape, the presence of lymphadenopathy, and pericardial effusion are highly indicative of thymic carcinomas.

4.
ACS Appl Mater Interfaces ; 12(2): 2152-2161, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31874020

RESUMO

Thermoradiotherapy acts as an important antitumor modality because heating can increase the blood flow and improve the oxygen level in tumor, thus remission of hypoxia-associated resistance for radiotherapy (RT). However, most agents for thermoradiotherapy are used either in the first near-infrared biological window or low photothermal conversion efficiency. Here, a facile method to prepare CuxS/Au nanocomposites via reduction methods from CuxS templates in mild synthetic conditions (i.e., aqueous solution and room temperature) is presented. After the growth of Au nanoparticles, the CuxS/Au nanocomposites have greater benefits for photothermal efficiency than that of CuxS nanoparticles due to the enhanced absorbance in the second near-infrared window. Moreover, biocompatibility and stability of these nanocomposites are greatly improved by lipoic acid poly(ethylene glycol). After the tumors were irradiated with a 1064 nm laser, their oxygenation status is subsequently improved, and the combination of photothermal therapy and RT achieves remarkable synergistic therapeutic effects. This work provides a novel idea to design a new-generation nanomedicine for tumor thermoradiotherapy.

5.
Front Neurol ; 10: 1083, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649618

RESUMO

Accumulating evidence from neuroimaging studies has supported that chronic pain could induce changes in brain function. However, few studies have focused on the dynamic regional homogeneity (dReHo) of trigeminal neuralgia (TN). In this study, twenty-eight TN patients and 28 healthy controls (HC) were included. Based on the resting-state fMRI (rsfMRI), we detected abnormalities in dReHo in the TN patients. Patients with TN had decreased dReHo in the left middle temporal gyrus, superior parietal lobule, and precentral gyrus, and increased dReHo in the thalamus. Furthermore, the increase in dReHo in the thalamus was positively correlated with duration of TN (r = 0.485, p = 0.012). These results provide compelling evidence for abnormal resting-state brain activity in TN and suggest that the duration of TN may play a critical role in brain function.

6.
Front Neurol ; 10: 1037, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632335

RESUMO

Objective: To explore whether or not functional connectivity (FC) could be used as a potential biomarker for classification of primary insomnia (PI) at the individual level by using multivariate pattern analysis (MVPA). Methods: Thirty-eight drug-naive patients with PI, and 44 healthy controls (HC) underwent resting-state functional MR imaging. Voxel-wise functional connectivity strength (FCS), large-scale functional connectivity (large-scale FC) and regional homogeneity (ReHo) were calculated for each participant. We used support vector machine (SVM) with the three types of metrics as features separately to classify patients from healthy controls. Then we evaluated its classification performances. Finally, FC metrics with significant high classification performance were compared between the two groups and were correlated with clinical characteristics, i.e., Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) in the patients' group. Results: The best classifier could reach up to an accuracy of 81.5%, with a sensitivity of 84.9%, specificity of 79.1%, and area under the receiver operating characteristic curve (AUC) of 83.0% (all P < 0.001). Right anterior insular cortex (BA48), left precuneus (BA7), and left middle frontal gyrus (BA8) showed high classification weights. In addition, the right anterior insular cortex (BA48) and left middle frontal gyrus (BA8) were the overlapping regions between MVPA and group comparison. Correlation analysis showed that FCS in left middle frontal gyrus and head of right caudate nucleus were correlated with PSQI and SDS, respectively. Conclusion: The current study suggests abnormal FCS in right anterior insular cortex (BA48) and left middle frontal gyrus (BA8) might serve as a potential neuromarkers for PI.

7.
Neuroimage Clin ; 24: 101951, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374398

RESUMO

OBJECTIVES: The present study explored the changes in spontaneous regional activity in post-traumatic stress disorder (PTSD) patients, who experienced severe traffic accidents. METHODS: 20 drug-naive PTSD patients and 18 healthy control subjects were imaged using resting-state functional magnetic resonance imaging (rs-fMRI) and analyzed by the algorithm of regional homogeneity (ReHo). RESULTS: Compared to the healthy control group, the PTSD group showed decreased ReHo values in the right angular gyrus. In addition, a negative correlation was found between the activity level of the angular gyrus and the CAPS score. CONCLUSION: The dysfunctions were found in the memory- and emotion-related areas, suggested a possible mechanism of memory dysregulation that might be related to the intrusive memory symptoms of PTSD. These results provided imaging evidence that might provide an in-depth understanding of the intrinsic functional architecture of PTSD.

8.
Front Neurosci ; 13: 806, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427923

RESUMO

Neuroimaging studies have shown that autism spectrum disorders (ASDs) may be associated with abnormalities in brain structures and functions at rest as well as during cognitive tasks. However, it remains unclear if functional connectivity (FC) of all brain neural networks is also changed in these subjects. In this study, we acquired functional magnetic resonance imaging scans from 93 children with ASD and 79 matched healthy subjects. Group independent component analysis was executed for all of the participants to estimate FC. One-sample t-tests were then performed to obtain the networks for each group. Group differences in the different brain networks were tested using two-sample t-tests. Finally, relationships between abnormal FC and clinical variables were investigated with Pearson's correlation analysis. The results from one-sample t-tests revealed nine networks with similar spatial patterns in these two groups. When compared with the controls, children with ASD showed increased connectivity in the right dorsolateral superior frontal gyrus and left middle frontal gyrus (MFG) within the occipital pole network. Children with ASD also showed decreased connectivity in the left gyrus rectus, left middle occipital gyrus, right angular gyrus, right MFG and right inferior frontal gyrus (IFG), orbital part within the lateral visual network (LVN), the left IFG, right precuneus, and right angular gyrus within the left frontoparietal (cognition) network. Furthermore, the mean FC values within the LVN showed significant positive correlations with total score of the Childhood Autism Rating Scale. Our findings indicate that abnormal FC extensively exists within some networks in children with ASD. This abnormal FC may constitute a biomarker of ASD. Our results are an important contribution to the study of neuropathophysiological mechanisms in children with ASD.

9.
Exp Ther Med ; 17(6): 4379-4388, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31105778

RESUMO

The present study investigated the role of energy loss assessed by vector flow mapping (VFM) in patients with hypertrophic cardiomyopathy (HCM). VFM analysis was performed in 42 patients with HCM and in 40 control subjects, which were matched for age, sex and left ventricular (LV) ejection fraction. The intra-LV and left atrial blood flow were obtained from the apical 3-chamber view, and the energy loss (EL) during the systolic and diastolic phases was calculated. The measurements were averaged over three cardiac cycles and indexed to body surface area. Compared with the controls, the left ventricular energy loss (LVEL)-total value was significantly decreased in patients with HCM during the diastolic phase (P1, P2 and P3; all P<0.05). A tendency for increased systolic LVEL-total values was observed in the patients with HCM compared with the controls (P>0.05). LVEL-base values were decreased in the patients with HCM during P1 and P2 (slow filling time). Compared with the controls, patients with HCM had lower LVEL-mid values during the diastolic phases (P0, P1, P2 and P3; all P<0.05). However, the LVEL-mid value of patients with HCM was higher compared with that of the controls during systolic P5 (P<0.05). LVEL-apex was decreased in patients with HCM during P0, P2 and P3. Compared with the controls, the left atrial energy loss (LAEL) of all three phases in patients with HCM were lower (each P<0.01). The diastolic LVEL values were significantly lower in patients with HCM compared with the controls; however, the systolic LVEL levels tended to be higher in HCM. The LAEL of the reservoir phase, conduit phase and atrial systolic phase were decreased in HCM compared with controls. The present study demonstrated that measurement of EL by VFM is a sensitive method of determining subclinical LV dysfunction in patients with HCM. The value of EL has been considered to be a quantitative parameter for the estimation of the efficiency of intraventricular blood flow.

10.
Bioconjug Chem ; 30(5): 1314-1322, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31034212

RESUMO

Prostate cancer is a heterogeneous disease with a poor survival rate at late stage. In this report, a dual targeting PET agent was developed to partially address the tumor heterogeneity issue. The heterodimer F-BCN-PSMA-NT was designed to target PSMA and neurotensin receptor1 (NTR1), both of which have demonstrated great potential in prostate cancer management. The heterodimer was synthesized through the conjugation of Glu-urea-lys(Ahx) (PSMA targeting motif) and NT20.3 (NTR1 targeting motif) to a symmetric trifunctional linker, bearing an azide group for further modification. Radio-labeling was performed using strain promoted azide-alkyne click reaction with high yield. Cell based assays suggested that F-BCN-PSMA-NT has comparable or only slightly reduced binding affinity with the corresponding monomers. Small animal PET clearly demonstrated that the heterodimer probe has prominent uptake not only in NTR1 positive/PSMA negative PC-3 tumors (1.4 ± 0.3%ID/g), but also in the PSMA positive/NTR1 negative LnCap tumors (1.3 ± 0.2%ID/g). The tracer showed comparable tumor to background ratio with each monomer. In summary, prostate cancer is a heterogeneous disease in need of improved diagnostics and treatments. The PSMA-NT heterodimer represents a new class of molecules that can be used to target two distinct antigens related to prostate cancer. In addition to the imaging applications demonstrated in this study, the agent also holds great potential on the treatment of heterogeneous prostate cancer.


Assuntos
Antígenos de Superfície/química , Glutamato Carboxipeptidase II/química , Neoplasias da Próstata/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Dimerização , Xenoenxertos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Receptores de Neurotensina
11.
Front Psychiatry ; 10: 234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031661

RESUMO

Posttraumatic stress disorder (PTSD) is a psychiatric condition that can emerge after exposure to an exceedingly traumatic event. Previous neuroimaging studies have indicated that PTSD is characterized by aberrant resting-state functional connectivity (FC). However, few existing studies on PTSD have examined dynamic changes in resting-state FC related to network formation, interaction, and dissolution over time. In this study, we compared the dynamic resting-state local and large-scale FC between PTSD patients (n = 22) and healthy controls (HC; n = 22; conducted as standard deviation in resting-state local and large-scale FC over a series of sliding windows). Local dynamic FC was examined by calculating the dynamic regional homogeneity (dReHo), and large-scale dynamic FC (dFC) was investigated between regions with significant dReHo group differences. For the PTSD patients, we also investigated the relationship between symptom severity and dFC/dReHo. Our results showed that PTSD patients were characterized by I) increased dynamic (more variable) dReHo in left precuneus (PCu); II) increased dynamic (more variable) dFC between the left PCu and left insula; and III) decreased dFC between left PCu and left inferior parietal lobe (IPL), and decreased dFC between left PCu and right PCu. However, there is no significant correlation between the clinical indicators and dReHo/dFC after the family-wise-error (FWE) correction. These findings provided the initial evidence that PTSD is characterized by aberrant patterns of fluctuating communication within brain system such as the default mode network (DMN) and among different brain systems such as the salience network and the DMN.

12.
Zhongguo Zhong Yao Za Zhi ; 44(5): 920-926, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989850

RESUMO

Anthraquinones,dianthrones and tannins are the main active ingredients of Rheum tanguticum. In this study the three components were determined by HPLC,and the results were analyzed by multiple comparisons,principal components analysis(PCA)and correspondence analysis(CA). The results showed that the contents of components in different growing areas and types(wild and cultivated) reached a significant level(P<0. 05). Baiyu county,Xiaojin county and Ruoergai county had obvious advantages in the accumulation of catechin hydrate,rhien and sensenoside A respectively. The principal component was different in two growing type and the wild environment was conducive to combined anthraquinones accumulation. For active components,normalized planting was better than retail cultivating. Therefore,the effect on the accumulation of chemical components in Rh. tangusticum,should be taken into full account in the selection of the cultural base of Rh. tanguticum. The standardized cultivating is superior to retail cultivating in terms of the accumulation of active ingredients,and standardized planting is inferior to the wild.


Assuntos
Antraquinonas/análise , Rheum/química , Taninos/análise , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Compostos Fitoquímicos/análise , Plantas Medicinais/química
13.
Eur Radiol ; 29(11): 5901-5909, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30980125

RESUMO

OBJECTIVES: The study aimed to explore the effects of codeine-containing cough syrup (CCS) exposure on cortical morphology and the relationship between cortical characteristics and CCS dependence. METHODS: Cortical morphometry based on Computational Anatomy Toolbox (CAT12) was used to compare changes in sulcal depth, gyrification, and cortical thickness of the cerebral cortex from 40 CCS users and 40 healthy controls (HCs) with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between abnormal cortical morphological changes and the duration of CCS use, impulsivity traits, and age of first use were investigated with correlation analysis (p < 0.05, uncorrected). RESULTS: CCS users exhibited significantly increased sulcal depth in the bilateral insula, bilateral lingual, bilateral superior frontal, right precuneus, and right middle frontal regions; increased gyrification in the right precentral cortex; and increased cortical thickness in the bilateral precentral, bilateral precuneus, and right superior temporal cortices compared to HCs. In addition, we found significant correlations between the bilateral insula, right superior frontal cortex, and right precentral gyrus and Barratt Impulsiveness Scale (BIS) total scores. CONCLUSIONS: Chronic CCS abuse may be associated with aberrant sulcal depth, gyrification, and cortical thickness. These morphological changes might serve as an underlying neurobiological mechanism of impulsive behavior in the CCS users. KEY POINTS: • Cortical morphological changes were detected in CCS users. • Increased sulcal depth, gyrification, and cortical thickness of some regions were found in the CCS users. • Positive correlations between cortical morphological changes and BIS total scores were identified.


Assuntos
Córtex Cerebral/patologia , Codeína/farmacologia , Tosse/diagnóstico , Lobo Frontal/patologia , Imagem por Ressonância Magnética/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Córtex Cerebral/efeitos dos fármacos , Tosse/tratamento farmacológico , Feminino , Lobo Frontal/efeitos dos fármacos , Humanos , Masculino , Adulto Jovem
14.
Aging (Albany NY) ; 11(1): 240-248, 2019 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-30636724

RESUMO

Metformin is a hypoglycemic agent used clinically in the treatment of type 2 diabetics. In addition, metformin is being investigated as a potential geroprotector. Here, we investigated the effects of metformin silkworm lifespan and the underlying molecular pathways involved. We found that metformin prolonged the lifespan of the male silkworm without reducing body weight, which suggests metformin can increase lifespan through remodeling of the animal's energy distribution strategy. Consistent with that idea, metformin reduced silk production and thus the energy devoted to that process. Metformin also increased fasting tolerance and levels of the antioxidant glutathione, and also activated an adenosine monophosphate-activated protein kinase-p53-forkhead box class O signaling pathway in silkworm. These results suggest that activity in this pathway may contribute to metformin-induced lifespan extension in silkworm by increasing stress resistance and antioxidative capacity while reducing energy output for silk product. The results also show that the silkworm is a potential useful animal model for evaluating the effects of small molecules with potential clinical utility.

15.
J Affect Disord ; 246: 338-345, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30597294

RESUMO

BACKGROUND: Insomnia is frequently accompanied by the generalized anxiety disorder (GAD) but mostly fMRI studies investigated their aberrant functional connectivity (FC) without this issue. Recently, dynamic FC approach is prevailing to capture the time-varying fluctuations of spontaneous brain activities. Nevertheless, it is unclear how the dynamic FC characteristics are altered by insomnia in GAD. METHODS: We acquired resting state fMRI and neuropsychological tests for the 17 comorbid GAD with insomnia (GAD/IS), 15 GAD and 24 healthy controls (HC). Then, based on the sliding window correlations, we estimated distinct brain states and statistically compared their dynamic properties. Further combining with graph theory, their network properties of each state among groups were accessed. Lastly, we examined associations between abnormal parameters and neuropsychological tests. RESULTS: We identified four brain states but did not observe significance on the state transitions. The mean dwell time and fraction of one globally hypoactive state accounted for high proportion of brain activities were significantly different (GAD > HC > GAD/IS). Meanwhile, we found gradual decreases in a brain state representing slight sleep/drowsiness (HC > GAD/IS > GAD). Additionally, we observed the GAD/IS patients had significantly increased network segregation and posterior cingulate cortex in a hyperarousal state, as well as significant associations with anxiety and insomnia severity. LIMITATIONS: The influences of depression on dynamic FC properties in GAD are unclear yet and more subjects should be recruited. CONCLUSIONS: These results provide new insights about the temporal features in GAD and offer potential biomarkers to evaluate the impacts of insomnia.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Adulto , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem
16.
Front Neurosci ; 12: 860, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532688

RESUMO

Purpose: Primary insomnia (PI) is the second most common mental disorder. However, the topologic alterations in structural brain connectome in patients with PI remain largely unknown. Methods: A total of 44 PI patients and 46 age-, gender-, and education level matched healthy control (HC) participants were recruited in this study. Diffusion tensor imaging (DTI) and resting state MRI were used to construct structural connectome for each participant, and the network parameters were employed by non-parametric permutations to evaluate the significant differences between the two groups. Relationships between abnormal network metrics and clinical characteristics, including the disease duration, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS), were investigated with Spearman's correlation analysis in PI patients. Results: PI patients demonstrated small-world architecture with lower global (P = 0.005) and local (P = 0.035) efficiencies compared with the HC group. The unique hub nodal properties in PI patients were mainly in the right limbic cortico-basal-ganglia circuit. Five disrupted subnetworks in PI patients were observed in the limbic cortico-basal-ganglia circuit and left default-mode networks (DMN) (P < 0.05, NBS corrected). Moreover, most unique hub nodal properties in the right limbic cortico-basal-ganglia circuit were significantly correlated with disease duration, and clinical characteristics (SAS, SDS, ISI scores) in PI processing. Conclusion: These findings suggested the abnormal anatomical network architecture may be closely linked to clinical characteristics in PI. The study provided novel insights into the neural substrates underlying symptoms and neurophysiologic mechanisms of PI.

17.
J Surg Res ; 231: 411-420, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30278961

RESUMO

BACKGROUND: The purpose of this study was to employ a novel ex vivo lung model of congenital diaphragmatic hernia (CDH) to determine how a mechanical compression affects early pulmonary development. METHODS: Day-15 whole fetal rat lungs (n = 6-12/group) from nitrofen-exposed and normal (vehicle only) dams were explanted and cultured ex vivo in compression microdevices (0.2 or 0.4 kPa) for 16 h to mimic physiologic compression forces that occur in CDH in vivo. Lungs were evaluated with significance set at P < 0.05. RESULTS: Nitrofen-exposed lungs were hypoplastic and expressed lower levels of surfactant protein C at baseline. Although compression alone did not alter the α-smooth muscle actin (ACTA2) expression in normal lungs, nitrofen-exposed lungs had significantly increased ACTA2 transcripts (0.2 kPa: 2.04 ± 0.15; 0.4 kPa: 2.22 ± 0.11; both P < 0.001). Nitrofen-exposed lungs also showed further reductions in surfactant protein C expression at 0.2 and 0.4 kPa (0.53 ± 0.04, P < 0.01; 0.69 ± 0.23, P < 0.001; respectively). Whereas normal lungs exposed to 0.2 and 0.4 kPa showed significant increases in periostin (POSTN), a mechanical stress-response molecule (1.79 ± 0.10 and 2.12 ± 0.39, respectively; both P < 0.001), nitrofen-exposed lungs had a significant decrease in POSTN expression (0.4 kPa: 0.67 ± 0.15, P < 0.001), which was confirmed by immunohistochemistry. CONCLUSIONS: Collectively, these pilot data in a model of CDH lung hypoplasia suggest a primary aberration in response to mechanical stress within the nitrofen lung, characterized by an upregulation of ACTA2 and a downregulation in SPFTC and POSTN. This ex vivo compression system may serve as a novel research platform to better understand the mechanobiology and complex regulation of matricellular dynamics during CDH fetal lung development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Hérnias Diafragmáticas Congênitas/embriologia , Pneumopatias/embriologia , Anormalidades do Sistema Respiratório/embriologia , Transcriptoma , Animais , Biomarcadores/metabolismo , Fenômenos Biomecânicos , Regulação para Baixo , Hérnias Diafragmáticas Congênitas/complicações , Técnicas In Vitro , Pneumopatias/etiologia , Pneumopatias/genética , Pneumopatias/metabolismo , Projetos Piloto , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Anormalidades do Sistema Respiratório/etiologia , Anormalidades do Sistema Respiratório/genética , Anormalidades do Sistema Respiratório/metabolismo , Regulação para Cima
18.
Neuropsychiatr Dis Treat ; 14: 1929-1939, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30122925

RESUMO

Purpose: The aim of this study is to investigate the morphology of cortical gray matter in patients with end-stage renal disease (ESRD) and the relationship between cortical thickness and kidney function. Patients and methods: Three-dimensional high-resolution brain structural magnetic resonance imaging data were collected from 35 patients with ESRD (28 men, 18-61 years old) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22-58 years old). Vertex-wise analysis was then performed to compare the brains of the patients with ESRD with those of HCs to identify abnormalities in the brains of the former. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability, and dialysis duration were correlated with brain morphometry alterations for the patients. Results: Patients with ESRD showed lesser cortical thickness than the HCs. The most significant cluster with decreased cortical thickness was found in the right prefrontal cortex (P<0.05, random-field theory correction). In addition, the four local peak vertices in the prefrontal cluster were lateral prefrontal cortex (Peaks 1 and 2), medial prefrontal cortex (Peak 3), and ventral prefrontal cortex (Peak 4). Significant negative correlations were observed between the cortical thicknesses of all four peak vertices and blood urea nitrogen; a negative correlation, between the cortical thickness in three of four peaks and serum creatinine; and a positive correlation, between cortical thickness in the medial prefrontal cortex (Peak 3) and hemoglobin. Conclusion: These results provided compelling evidence for cortical abnormality of ESRD patients and suggested that kidney function may be the key factor for predicting changes of brain tissue structure.

19.
Neuroimage Clin ; 19: 775-781, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29988765

RESUMO

Codeine-containing cough syrups (CCS) have become one of the most popular drugs of abuse in young population worldwide. However, the neurobiological mechanisms underlying CCS-dependence are yet ill-defined. Therefore, understanding the brain abnormalities in chronic users of CCS is crucial for developing effective interventions. The present study depicted the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in chronic users of CCS. In addition, the degree centrality (DC) changes were correlated to the Barratt Impulsiveness Scale (BIS-11) total score, dose, duration of CCS use, and the age at first use of cough syrups. The current study included 38 chronic CCS users and 34 matched control subjects. All patients were evaluated using the BIS-11. Next, resting-state functional magnetic resonance imaging (rs-fMRI) datasets were acquired from these CCS users and controls. Whole-brain connectivity was analyzed using a graph theory approach: degree centrality (DC). CCS-dependent individuals exhibited low DC values in the left inferior parietal lobule and the left middle temporal gyrus, while high DC values were noted in the right pallidum and the right hippocampus (P < 0.01, AlphaSim corrected). Also, significant correlations were established between average DC value in the left inferior parietal lobule and attentional impulsivity scores and the age at first CCS use. The rs-fMRI study suggested that the abnormal intrinsic dysconnectivity pattern of whole-brain functional networks may provide an insight into the neural substrates of abnormalities in the cognitive control circuit, the reward circuit, and the learning and memory circuit in CCS-dependent individuals.


Assuntos
Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico , Codeína , Feminino , Humanos , Comportamento Impulsivo/fisiologia , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/fisiopatologia , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Estudos Prospectivos
20.
Plant Physiol ; 178(1): 189-201, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29987002

RESUMO

4-Hydroxy-2,5-dimethyl-3(2H)-furanone is a major contributor to the aroma of strawberry (Fragaria × ananassa) fruit, and the last step in its biosynthesis is catalyzed by strawberry quinone oxidoreductase (FaQR). Here, an ethylene response factor (FaERF#9) was characterized as a positive regulator of the FaQR promoter. Linear regression analysis indicated that FaERF#9 transcript levels were correlated significantly with both FaQR transcripts and furanone content in different strawberry cultivars. Transient overexpression of FaERF#9 in strawberry fruit significantly increased FaQR expression and furaneol production. Yeast one-hybrid assays, however, indicated that FaERF#9 by itself did not bind to the FaQR promoter. An MYB transcription factor (FaMYB98) identified in yeast one-hybrid screening of the strawberry cDNA library was capable of both binding to the promoter and activating the transcription of FaQR by ∼5.6-fold. Yeast two-hybrid assay and bimolecular fluorescence complementation confirmed a direct protein-protein interaction between FaERF#9 and FaMYB98, and in combination, they activated the FaQR promoter 14-fold in transactivation assays. These results indicate that an ERF-MYB complex containing FaERF#9 and FaMYB98 activates the FaQR promoter and up-regulates 4-hydroxy-2,5-dimethyl-3(2H)-furanone biosynthesis in strawberry.


Assuntos
Fragaria/metabolismo , Furanos/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fragaria/genética , Frutas/genética , Frutas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Complexos Multiproteicos/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica , Fatores de Transcrição/genética , Técnicas do Sistema de Duplo-Híbrido
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