53 results on '"Nan, Jie"'
Search Results
2. Aberrant miR-339-5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice
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Hao-Yu Zou, Lin Guo, Bei Zhang, Si Chen, Xin-Rong Wu, Xian-Dong Liu, Xin-Yu Xu, Bin-Yin Li, Shengdi Chen, Nan-Jie Xu, and Suya Sun
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Cell biology ,Neuroscience ,Medicine - Abstract
Mushroom spine loss and calcium dyshomeostasis are early hallmark events of age-related neurodegeneration, such as Alzheimer’s disease (AD), that are connected with neuronal hyperactivity in early pathology of cognitive brain areas. However, it remains elusive how these key events are triggered at the molecular level for the neuronal abnormality that occurs at the initial stage of disease. Here, we identify downregulated miR-339-5p and its upregulated target protein, neuronatin (Nnat), in cortex neurons from the presenilin-1 M146V knockin (PSEN1-M146V KI) mouse model of familial AD (FAD). Inhibition of miR-339-5p or overexpression of Nnat recapitulates spine loss and endoplasmic reticulum calcium overload in cortical neurons with the PSEN1 mutation. Conversely, either overexpression of miR-339-5p or knockdown of Nnat restores spine morphogenesis and calcium homeostasis. We used fiber photometry recording during the object-cognitive process to further demonstrate that the PSEN1 mutant causes defective habituation in neuronal reaction in the retrosplenial cortex and that this can be rescued by restoring the miR-339-5p/Nnat pathway. Our findings thus reveal crucial roles of the miR-339-5p/Nnat pathway in FAD that may serve as potential diagnostic and therapeutic targets for early pathogenesis.
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- 2022
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3. Thermal Conductivity Performance of Polypropylene Composites Filled with Polydopamine-Functionalized Hexagonal Boron Nitride.
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Lin Chen, Hong-Fei Xu, Shao-Jian He, Yi-Hang Du, Nan-Jie Yu, Xiao-Ze Du, Jun Lin, and Sergei Nazarenko
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Medicine ,Science - Abstract
Mussel-inspired approach was attempted to non-covalently functionalize the surfaces of boron nitride (BN) with self-polymerized dopamine coatings in order to reduce the interfacial thermal barrier and enhance the thermal conductivity of BN-containing composites. Compared to the polypropylene (PP) composites filled with pristine BN at the same filler content, thermal conductivity was much higher for those filled with both functionalized BN (f-BN) and maleic anhydride grafted PP (PP-g-ma) due to the improved filler dispersion and better interfacial filler-matrix compatibility, which facilitated the development of more thermal paths. Theoretical models were also applied to predict the composite thermal conductivity in which the Nielsen model was found to fit well with the experimental results, and the estimated effective aspect ratio of fillers well corresponded to the degree of filler aggregation as observed in the morphological study.
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- 2017
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4. Deep learning–based methods may minimize GBCA dosage in brain MRI
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Cheng Xu, Jing Xue, Jonthan Tamir, Huanyu Luo, Tao Zhou, Fuqing Zhou, Nan-Jie Gong, Yunyun Duan, Srivathsa Pasumarthi Venkata, Greg Zaharchuk, Tao Zhang, and Yaou Liu
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medicine.medical_specialty ,medicine.diagnostic_test ,Image quality ,business.industry ,Deep learning ,Ultrasound ,Magnetic resonance imaging ,Interventional radiology ,General Medicine ,030218 nuclear medicine & medical imaging ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Brain mri ,Radiology, Nuclear Medicine and imaging ,Radiology ,Artificial intelligence ,medicine.symptom ,business ,Neuroradiology - Abstract
To evaluate the clinical performance of a deep learning (DL)–based method for brain MRI exams with reduced gadolinium-based contrast agent (GBCA) dose to provide better understanding of the readiness and limitations of this method. Eighty-three consecutive patients (from March 2019 to August 2019) who underwent brain contrast-enhanced (CE) MRI were included. Three 3D T1-weighted images with zero-dose, low-dose (10%), and full-dose (100%) GBCA were collected. The first 30 cases were used to train a DL model to synthesize the full-dose GBCA images from the zero-dose and low-dose image pairs. The remaining 53 cases were used for testing. The enhancement pattern, number, and location of enhancing lesions were recorded. Overall image quality, image signal noise ratio (SNR), lesion conspicuity, and lesion enhancement were assessed. Lesion detection from the DL-synthesized CE-MRI image accurately matched those from the true full-dose CE-MRI images in 48 of 53 cases (90.6%). The DL method identified the lesions in 34 of 36 cases (94.4%) with a single enhanced lesion and all lesions in 3 of 6 cases (50.0%) in cases with multiple enhancing lesions. The agreement between synthesized and true full-dose CE-MRI images were 0.73, 0.63, 0.89, and 0.87 for image quality, image SNR, lesion conspicuity, and lesion enhancement, respectively. The proposed DL method is a feasible way to minimize the dosage of GBCAs in brain MRI without sacrificing the diagnostic information. Missing enhancement of small lesions in patients with multiple lesions was observed, requiring improvements in algorithms or dosage design. • This study evaluated the clinical performance of a DL-based reconstruction method for significant dose reduction in GBCA contrast-enhanced MRI exams. • The proposed DL method has the potential to satisfy the routine radiological diagnosis needs in certain clinical applications.
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- 2021
5. Targeting neuroplasticity in patients with neurodegenerative diseases using brain stimulation techniques
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Wei-Guang Li, Tian-Le Xu, Ti-Fei Yuan, Chencheng Zhang, Hongjiang Wei, Nan-Jie Xu, Jun Liu, and Suya Sun
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0301 basic medicine ,medicine.medical_specialty ,Deep brain stimulation ,Neurology ,Parkinson's disease ,Deep Brain Stimulation ,Cognitive Neuroscience ,medicine.medical_treatment ,Review ,Disease ,Synaptic plasticity ,lcsh:RC346-429 ,Stereotaxic Techniques ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Alzheimer Disease ,Neuroplasticity ,Animals ,Humans ,Medicine ,Neurotransmitter ,lcsh:Neurology. Diseases of the nervous system ,Neuronal Plasticity ,business.industry ,Brain ,Neurodegenerative Diseases ,Parkinson Disease ,medicine.disease ,Transcranial Magnetic Stimulation ,Synapse ,Transcranial magnetic stimulation ,030104 developmental biology ,Brain stimulation ,Parkinson’s disease ,Neurology (clinical) ,business ,Neuroscience ,Alzheimer’s disease ,030217 neurology & neurosurgery - Abstract
Deficits in synaptic transmission and plasticity are thought to contribute to the pathophysiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Several brain stimulation techniques are currently available to assess or modulate human neuroplasticity, which could offer clinically useful interventions as well as quantitative diagnostic and prognostic biomarkers. In this review, we discuss several brain stimulation techniques, with a special emphasis on transcranial magnetic stimulation and deep brain stimulation (DBS), and review the results of clinical studies that applied these techniques to examine or modulate impaired neuroplasticity at the local and network levels in patients with AD or PD. The impaired neuroplasticity can be detected in patients at the earlier and later stages of both neurodegenerative diseases. However, current brain stimulation techniques, with a notable exception of DBS for PD treatment, cannot serve as adequate clinical tools to assist in the diagnosis, treatment, or prognosis of individual patients with AD or PD. Targeting the impaired neuroplasticity with improved brain stimulation techniques could offer a powerful novel approach for the treatment of AD and PD.
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- 2020
6. EphB2 mediates social isolation-induced memory forgetting
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Xian-Dong Liu, Suya Sun, Wu-Bo Han, Xin-Rong Wu, Nan-Jie Xu, and Yu Zhang
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0301 basic medicine ,China ,Memory, Long-Term ,Receptor, EphB2 ,Hippocampus ,Molecular neuroscience ,Biology ,Receptor tyrosine kinase ,Article ,lcsh:RC321-571 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Memory ,Neuroplasticity ,medicine ,Animals ,Social isolation ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Biological Psychiatry ,Memory Disorders ,Forgetting ,Neuronal Plasticity ,Glutamate receptor ,Psychiatry and Mental health ,030104 developmental biology ,Social Isolation ,Synaptic plasticity ,biology.protein ,medicine.symptom ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Social isolation in adolescence leads to lasting deficits, including emotional and cognitive dysregulation. It remains unclear, however, how social isolation affects certain processes of memory and what molecular mechanisms are involved. In this study, we found that social isolation during the post-weaning period resulted in forgetting of the long-term fear memory, which was attributable to the downregulation of synaptic function in the hippocampal CA1 region mediated by EphB2, a receptor tyrosine kinase which involves in the glutamate receptor multiprotein complex. Viral-mediated EphB2 knockdown in CA1 mimicked the memory defects in group-housed mice, whereas restoration of EphB2 by either viral overexpression or resocialization reversed the memory decline in isolated mice. Taken together, our finding indicates that social isolation gives rise to memory forgetting by disrupting EphB2-mediated synaptic plasticity, which may provide a potential target for preventing memory loss caused by social isolation or loneliness.
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- 2020
7. Effects of seasonal variation on soil microbial community structure and enzyme activity in a Masson pine forest in Southwest China
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Qing-ping Zeng, Nan-jie Li, Binghui He, Lei Yang, and Song-ping Luo
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Global and Planetary Change ,Pinus massoniana ,010504 meteorology & atmospheric sciences ,biology ,Geography, Planning and Development ,Geology ,Seasonality ,010502 geochemistry & geophysics ,biology.organism_classification ,medicine.disease ,01 natural sciences ,Enzyme assay ,Agronomy ,Microbial population biology ,Canonical correspondence analysis ,Soil pH ,biology.protein ,medicine ,Ecosystem ,Water content ,0105 earth and related environmental sciences ,Nature and Landscape Conservation ,Earth-Surface Processes - Abstract
Soil microbial communities and enzyme activities play key roles in soil ecosystems. Both are sensitive to changes in environmental factors, including seasonal temperature, precipitation variations and soil properties. To understand the interactive mechanisms of seasonal changes that affect soil microbial communities and enzyme activities in a subtropical masson pine (Pinus massoniana) forest, we investigated the soil microbial community structure and enzyme activities to identify the effect of seasonal changes on the soil microbial community for two years in Jinyun Mountain National Nature Reserve, Chongqing, China. The soil microbial community structure was investigated using phospholipid fatty acids (PLFAs). The results indicated that a total of 36 different PLFAs were identified, and 16:0 was found in the highest proportions in the four seasons, moreover, the total PLFAs abundance were highest in spring and lowest in winter. Bacteria and actinomycetes were the dominant types in the study area. Seasonal changes also had a significant (P < 0.05) influence on the soil enzyme activity. The maximum and minimum values of the invertase and catalase activities were observed in autumn and winter, respectively. However, the maximum and minimum values of the urease and phosphatase acid enzymatic activities were found in spring and winter, respectively. Canonical correspondence analysis (CCA) analysis revealed that the seasonal shifts in soil community composition and enzyme activities were relatively more sensitive to soil moisture and temperature, but the microbial community structure and enzyme activity were not correlated with soil pH in the study region. This study highlights how the seasonal variations affect the microbial community and function (enzyme activity) to better understand and predict microbial responses to future climate regimes in subtropical area.
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- 2020
8. Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice
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Xian-Dong Liu, Xiao-Na Zhu, Sheng-Di Chen, Dong-Fu Feng, Nan-Jie Xu, Yuan-Bo Pan, Si Chen, Suya Sun, and Peng-Hui Ai
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Neurology ,Time Factors ,Cognitive Neuroscience ,Prodromal Symptoms ,Mice, Transgenic ,Paroxetine treatment ,Disease ,Irritability ,Neuroprotection ,Receptors, N-Methyl-D-Aspartate ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,Presenilin-1 ,Medicine ,Animals ,Apathy ,Affective Symptoms ,Memory deficit ,Depression (differential diagnoses) ,lcsh:Neurology. Diseases of the nervous system ,Memory Disorders ,business.industry ,Research ,Glutamate receptor ,Paroxetine ,030104 developmental biology ,Neuroprotective Agents ,Anxiety ,Neurology (clinical) ,medicine.symptom ,business ,Alzheimer’s disease ,030217 neurology & neurosurgery ,Selective Serotonin Reuptake Inhibitors ,medicine.drug - Abstract
Background Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer’s disease (AD), which might be an increased risk for later developing AD. Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor (SSRI) paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress. Methods To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress, we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age. Next, we tested the cognitive, biochemical and pathological, effects of long term administration of paroxetine at 6 months old. Results Our results showed that AD mice displayed emotional dysfunction in the early stage. Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice. Conclusion Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice. These neuroprotective effects are attributable to functional restoration of glutamate receptor (GluN2A) in AD mice.
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- 2020
9. Roles of physical exercise in neurodegeneration: reversal of epigenetic clock
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Nan-Jie Xu, Xian-Dong Liu, JiaYi Zhu, Ming-Ying Luo, and Miao Xu
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Aging ,medicine.medical_specialty ,Neurology ,Cognitive Neuroscience ,Physical exercise ,Review ,Motor deficits ,Epigenesis, Genetic ,Cellular and Molecular Neuroscience ,Neuroplasticity ,medicine ,Humans ,Epigenetics ,Neurodegeneration ,RC346-429 ,Exercise ,Neuroinflammation ,DNA methylation ,business.industry ,Brain ,dNaM ,Neurodegenerative Diseases ,Neural mechanism ,medicine.disease ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,business ,Neuroscience ,DNA Damage - Abstract
The epigenetic clock is defined by the DNA methylation (DNAm) level and has been extensively applied to distinguish biological age from chronological age. Aging-related neurodegeneration is associated with epigenetic alteration, which determines the status of diseases. In recent years, extensive research has shown that physical exercise (PE) can affect the DNAm level, implying a reversal of the epigenetic clock in neurodegeneration. PE also regulates brain plasticity, neuroinflammation, and molecular signaling cascades associated with epigenetics. This review summarizes the effects of PE on neurodegenerative diseases via both general and disease-specific DNAm mechanisms, and discusses epigenetic modifications that alleviate the pathological symptoms of these diseases. This may lead to probing of the underpinnings of neurodegenerative disorders and provide valuable therapeutic references for cognitive and motor dysfunction.
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- 2021
10. Microstructural alterations of cortical and deep gray matter over a season of high school football revealed by diffusion kurtosis imaging
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Nan-Jie Gong, Mark Sundman, Melissa A. Fraser, Samuel Kuzminski, Chunlei Liu, Kevin M. Guskiewicz, Jeffrey R. Petrella, and Michael Clark
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Male ,Adolescent ,Head impact ,Thalamus ,Football ,Poison control ,Biology ,Quantitative susceptibility mapping (QSM) ,Gray (unit) ,lcsh:RC321-571 ,030218 nuclear medicine & medical imaging ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Concussion ,medicine ,Humans ,Gray matter ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Diffusion Kurtosis Imaging ,Brain Concussion ,Cerebral Cortex ,Diffusion kurtosis imaging (DKI) ,Putamen ,Quantitative susceptibility mapping ,Anatomy ,medicine.disease ,Diffusion Tensor Imaging ,Neurology ,Seasons ,030217 neurology & neurosurgery - Abstract
Objectives To probe microstructural changes that are associated with subconcussive head impact exposure in deep and cortical gray matter of high school football players over a single season. Methods Players underwent diffusion kurtosis imaging (DKI) and quantitative susceptibility mapping (QSM) scans. Head impact data was recorded. Association between parametric changes and frequency of frontal head impact was assessed. Results In deep gray matter, significant decreases in mean kurtosis (MK) and increases in mean diffusivity (MD) over the season were observed in the thalamus and putamen. Correlations between changes in DKI metrics and frequency of frontal impacts were observed in the putamen and caudate. In cortical gray matter, decreases in MK were observed in regions including the pars triangularis and inferior parietal. In addition, increases in MD were observed in the rostral middle frontal cortices. Negative correlations between MK and frequency of frontal impacts were observed in the posterior part of the brain including the pericalcarine, lingual and middle temporal cortices. Magnetic susceptibility values exhibited no significant difference or correlation, suggesting these diffusion changes common within the group may not be associated with iron-related mechanisms. Conclusion Microstructural alterations over the season and correlations with head impacts were captured by DKI metrics, which suggested that DKI imaging of gray matter may yield valuable biomarkers for evaluating brain injuries associated with subconcussive head impact. Findings of associations between frontal impacts and changes in posterior cortical gray matter also indicated that contrecoup injury rather than coup injury might be the dominant mechanism underlying the observed microstructural alterations. Advances in knowledge Significant microstructural changes, as reflected by DKI metrics, in cortical gray matter such as the rostral middle frontal cortices, and in deep gray matter such as the thalamus were observed in high school football players over the course of a single season without clinically diagnosed concussion. QSM showed no evidence of iron-related changes in the observed subconcussive brain injuries. The detected microstructural changes in cortical and deep gray matter correlated with frequency of subconcussive head impacts. Implications for patient care DKI may yield valuable biomarkers for evaluating the severity of brain injuries associated with subconcussive head impacts in contact sport athletes.
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- 2018
11. Input associativity underlies fear memory renewal
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Qi Wang, Nan-Jie Xu, Tian-Le Xu, Hui-Ran Fan, Xin Yi, Han Xu, Xue Gu, Ying Li, Yan-Jiao Wu, Ti-Fei Yuan, Jia-Jie Zhu, Michael X. Zhu, Qin Wang, Wei-Guang Li, Jiangteng Lu, and Qin Jiang
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Multidisciplinary ,input associativity ,AcademicSubjects/SCI00010 ,Hippocampus ,Long-term potentiation ,Optogenetics ,memory ensembles ,Auditory cortex ,Amygdala ,Associative learning ,lateral amygdala ,medicine.anatomical_structure ,Hebbian theory ,fear renewal ,medicine ,auditory cortex ,Fear conditioning ,AcademicSubjects/MED00010 ,Psychology ,ventral hippocampus ,Neuroscience ,long-term potentiation ,Research Article - Abstract
Synaptic associativity, a feature of Hebbian plasticity wherein coactivation of two inputs onto the same neuron produces synergistic actions on postsynaptic activity, is a primary cellular correlate of associative learning. However, whether and how synaptic associativity are implemented into context-dependent relapse of extinguished memory (i.e. fear renewal) is unknown. Here, using an auditory fear conditioning paradigm in mice, we show that fear renewal is determined by the associativity between convergent inputs from the auditory cortex (ACx) and ventral hippocampus (vHPC) onto the lateral amygdala (LA) that reactivate ensembles engaged during learning. Fear renewal enhances synaptic strengths of both ACx to LA and the previously unknown vHPC to LA monosynaptic inputs. While inactivating either of the afferents abolishes fear renewal, optogenetic activation of their input associativity in the LA recapitulates fear renewal. Thus, input associativity underlies fear memory renewal.
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- 2021
12. Evaluating Heterogeneity of Primary Lung Tumor Using Clinical Routine Magnetic Resonance Imaging and a Tumor Heterogeneity Index
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Nan Hu, ShaoHan Yin, Qiwen Li, Haoqiang He, Linchang Zhong, Nan-Jie Gong, Jinyu Guo, Peiqiang Cai, Chuanmiao Xie, Hui Liu, and Bo Qiu
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Cancer Research ,medicine.medical_treatment ,T stage ,radiation therapy ,lcsh:RC254-282 ,Tumor heterogeneity ,030218 nuclear medicine & medical imaging ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,medicine ,non-small cell lung cancer ,Original Research ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Primary tumor ,Radiation therapy ,Oncology ,030220 oncology & carcinogenesis ,T-stage ,Lung tumor ,heterogeneity ,business ,Nuclear medicine ,MRI - Abstract
ObjectiveTo improve the assessment of primary tumor heterogeneity in magnetic resonance imaging (MRI) of non-small cell lung cancer (NSCLC), we proposed a method using basic measurements from T1- and T2-weighted MRI.MethodsOne hundred and four NSCLC patients with different T stages were studied. Fifty-two patients were analyzed as training group and another 52 as testing group. The ratios of standard deviation (SD)/mean signal value of primary tumor from T1-weighted (T1WI), T1-enhanced (T1C), T2-weighted (T2WI), and T2 fat suppression (T2fs) images were calculated. In the training group, correlation analyses were performed between the ratios and T stages. Then an ordinal regression model was built to generate the tumor heterogeneous index (THI) for evaluating the heterogeneity of tumor. The model was validated in the testing group.ResultsThere were 11, 32, 40, and 21 patients with T1, T2, T3, and T4 disease, respectively. In the training group, the median SD/mean on T1WI, T1C, T2WI, and T2fs sequences was 0.11, 0.19, 0.16, and 0.15 respectively. The SD/mean on T1C (p=0.003), T2WI (p=0.000), and T2fs sequences (p=0.002) correlated significantly with T stages. Patients with more advanced T stage showed higher SD/mean on T2-weighted, T2fs, and T1C sequences. The median THI in the training group was 2.15. THI correlated with T stage significantly (p=0.000). In the testing group, THI was also significantly related to T stages (p=0.001). Higher THI had relevance to more advanced T stage.ConclusionsThe proposed ratio measurements and THI based on MRI can serve as functional radiomic markers that correlated with T stages for evaluating heterogeneity of lung tumors.
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- 2021
13. Imaging microstructure with diffusion and susceptibility MR: neuronal density correlation in Disrupted‐in‐Schizophrenia‐1 mutant mice
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Eric J. Benner, Chunlei Liu, Mikhail V. Pletnikov, Nan-Jie Gong, and Russell Dibb
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Neurite ,Hippocampus ,Cell Count ,Mice, Transgenic ,Nerve Tissue Proteins ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,DISC1 ,0302 clinical medicine ,Nuclear magnetic resonance ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Diffusion Kurtosis Imaging ,Spectroscopy ,Neurons ,biology ,Chemistry ,Magnetic Phenomena ,Quantitative susceptibility mapping ,Mice, Mutant Strains ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,nervous system ,Cerebral cortex ,biology.protein ,Kurtosis ,Molecular Medicine ,Neuroglia ,030217 neurology & neurosurgery - Abstract
Purpose To probe cerebral microstructural abnormalities and assess changes of neuronal density in Disrupted-in-Schizophrenia-1 (DISC1) mice using non-Gaussian diffusion and quantitative susceptibility mapping (QSM). Materials and methods Brain specimens of transgenic DISC1 mice (n = 8) and control mice (n = 7) were scanned. Metrics of neurite orientation dispersion and density imaging (NODDI) and diffusion kurtosis imaging (DKI), as well as QSM, were acquired. Cell counting was performed on Nissl-stained sections. Group differences of imaging metrics and cell density were assessed. Pearson correlations between imaging metrics and cell densities were also examined. Results Significant increases of neuronal density were observed in the hippocampus of DISC1 mice. DKI metrics such as mean kurtosis exhibited significant group differences in the caudate putamen (P = 0.015), cerebral cortex (P = 0.021), and hippocampus (P = 0.011). However, DKI metrics did not correlate with cell density. In contrast, significant positive correlation between density of neurons and the neurite density index of NODDI in the hippocampus was observed (r = 0.783, P = 0.007). Significant correlation between density of neurons and susceptibility (r = 0.657, P = 0.039), as well as between density of neuroglia and susceptibility (r = 0.750, P = 0.013), was also observed in the hippocampus. Conclusion The imaging metrics derived from DKI were not sensitive specifically to cell density, while NODDI could provide diffusion metrics sensitive to density of neurons. The magnetic susceptibility values derived from the QSM method can serve as a sensitive biomarker for quantifying neuronal density.
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- 2020
14. Morphological and molecular alterations of reactive astrocytes without proliferation in cerebral cortex of an APP/PS1 transgenic mouse model and Alzheimer's patients
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Pi‐Fang Gong, Jia‐Tong Li, Song Qin, Nan‐Jie Xu, and Kun‐Yu Li
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0301 basic medicine ,Genetically modified mouse ,Mice, Transgenic ,Pathogenesis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,Alzheimer Disease ,Glutamine synthetase ,Cortex (anatomy) ,mental disorders ,medicine ,Presenilin-1 ,Animals ,Humans ,Cell Proliferation ,Cerebral Cortex ,Amyloid beta-Peptides ,Glial fibrillary acidic protein ,biology ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Cerebral cortex ,Astrocytes ,biology.protein ,Signal transduction ,030217 neurology & neurosurgery ,Homeostasis - Abstract
Astrocytes are fundamental for maintaining brain homeostasis and are commonly involved in the progression of neurodegenerative diseases including Alzheimer's disease (AD). In response to injury or toxic material, astrocytes undergo activation that results in hypertrophy and process ramification. Although numerous studies have shown that reactive astrocytes are intimately related to the pathogenesis of AD, their characteristic features including morphological and molecular alterations that occur during different stages of AD progression remain to be elucidated. Here, we crossed astrocyte-specific reporter mice hGFAP-CreERT2;Rosa-tdTomato with APP/PS1 mice, and then used genetic tracing to characterize the morphological profiles and expression of molecular biomarkers associated with progressive β-amyloid deposits in the cortical region of AD mice. Expression of glutamine synthetase (GS) was lower in cortical reactive astrocytes, in contrast to the higher expression of glial fibrillary acidic protein, of APP/PS1 mice and AD patients relative to that in cortical astrocytes of wild-type mice and age-matched controls, respectively. GS activity was also decreased obviously in the cortex of APP/PS1 mice at 6 and 12 months of age relative to that in the wild-type mice of the same ages. Furthermore, cortical reactive astrocytes in APP/PS1 mice and AD patients did not undergo proliferation. Finally, based on RNA-sequencing analysis, we identified differentially expressed transcripts of signal transduction molecules involved in early induction of reactive astrocytes in the cortex of APP/PS1 mice. These findings provide a morphological and molecular basis with which to understand the function and mechanism of reactive astrocytes in the progression of AD.
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- 2020
15. Editorial: Neuronal Development and Degeneration
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Wenbo Zhang, Patrice Fort, and Nan Jie Xu
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retina ,0303 health sciences ,Retina ,lcsh:QH426-470 ,business.industry ,brain ,degeneration ,Degeneration (medical) ,lcsh:Genetics ,03 medical and health sciences ,neurodegenerative disease ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,neuronal development ,Genetics ,medicine ,Molecular Medicine ,business ,Neuroscience ,Genetics (clinical) ,030304 developmental biology - Published
- 2019
16. Editorial: Neuronal Development and Degeneration
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Nan Jie Xu, Patrice E. Fort, and Wenbo Zhang
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Retina ,retina ,medicine.anatomical_structure ,Editorial ,neurodegenerative disease ,brain ,medicine ,Genetics ,neuronal development ,degeneration ,Degeneration (medical) ,Biology ,Neuroscience - Published
- 2019
17. The Influence of Activator Composition on the Strength, Shrinkage and Chloride Migration Resistance of Alkali-Activated Slag Mortars
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Nan Jie Hu, Hans-Carsten Kühne, Götz Hüsken, and Gregor J. G. Gluth
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Materials science ,020502 materials ,Mechanical Engineering ,0211 other engineering and technologies ,02 engineering and technology ,Microstructure ,Chloride ,Alkali activated slag ,law.invention ,Portland cement ,Compressive strength ,0205 materials engineering ,Mechanics of Materials ,law ,021105 building & construction ,Activator (phosphor) ,medicine ,General Materials Science ,Mortar ,Composite material ,Shrinkage ,medicine.drug - Abstract
Alkali-activated slag materials are known for their high chloride penetration resistance. This makes them potentially applicable as repair systems for damaged steel-reinforced concrete structures, which are exposed to chloride attack. For this purpose, the influence of the activator composition, i.e. the SiO2and Na2O concentration of the alkaline solution on a) the compressive strength, b) shrinkage and mass change and c) the resistance against chloride penetration of four alkali-activated slag mortars (AASM) were studied. An ordinary Portland cement-based mortar was used as the reference sample. Increasing SiO2and Na2O concentrations increased the strength, shrinkage and mass loss of the AASMs. The resistance of the mortars against chloride penetration was evaluated using the non-steady-state migration coefficient Dnssmobtained from NT BUILD 492. The results indicate that the Dnssmis related to differences in the pore solution of the AASMs rather than to differences in their microstructure. An upcoming study of the authors is going to evaluate this hypothesis by the accelerated chloride penetration (diffusion) test.
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- 2018
18. Differential microstructural and morphological abnormalities in mild cognitive impairment and Alzheimer's disease: Evidence from cortical and deep gray matter
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Lam-Ming Leung, Russell Dibb, Nan-Jie Gong, Chun-Sing Wong, Chun-Chung Chan, and Chunlei Liu
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Radiological and Ultrasound Technology ,business.industry ,Anatomy ,Mr imaging ,Gray (unit) ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Neurology ,Hum ,Medicine ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Cognitive impairment ,business ,Neuroscience ,Pathological ,Diffusion Kurtosis Imaging ,030217 neurology & neurosurgery ,Diffusion MRI - Abstract
One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc.
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- 2017
19. The activated newborn neurons participate in enriched environment induced improvement of locomotor function in APP/PS1 mice
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Hui-Dong Tang, Nan-Jie Xu, Qiongqiong Li, Hualong Wang, Jianqing Ding, Sheng-Di Chen, and Suya Sun
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Male ,medicine.medical_specialty ,Elevated plus maze ,Neurogenesis ,Hippocampus ,Mice, Transgenic ,Motor Activity ,050105 experimental psychology ,lcsh:RC321-571 ,03 medical and health sciences ,Behavioral Neuroscience ,Mice ,0302 clinical medicine ,Cognition ,Internal medicine ,Physical Stimulation ,Neuroplasticity ,mental disorders ,Medicine ,elevated plus maze ,Animals ,0501 psychology and cognitive sciences ,Maze Learning ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Research ,Neurons ,Environmental enrichment ,Behavior, Animal ,business.industry ,Dentate gyrus ,05 social sciences ,locomotor function ,Fear ,Alzheimer's disease ,Endocrinology ,nervous system ,Animals, Newborn ,Dentate Gyrus ,Models, Animal ,Conditioning ,business ,030217 neurology & neurosurgery ,enriched environment - Abstract
Introduction Alzheimer's disease (AD) is an age‐related neurodegenerative disorder. One of the pathological features of AD is neuronal loss in brain regions associated with cognition, particularly the hippocampus. An enriched environment (EE) can facilitate neuronal plasticity and improve behaviors such as emotion, motor function, and cognition in AD. Methods After APP/PS1 mice were exposed to EE at an early stage (2 months of age), elevated plus maze performance and contextual fear conditioning were tested, and neurogenesis and the extent of activation in the hippocampus were observed. Results The results showed that, compared with that in the mice that experienced a standard environment, the cognition of the mice exposed to EE, as measured by contextual fear conditioning, was not statistically significant. However, based on their performance in the elevated plus maze, the index was increased in the mice, especially the APP/PS1 mice, exposed to EE. Consistent with the behavioral changes, the APP/PS1 mice exposed to EE showed an increased number of c‐Fos‐positive neurons and elevated neurogenesis in the dentate gyrus (DG) area. In addition, the activation of newborn neurons did not occur in the other three groups. Conclusions These results indicate that the activation of newborn neurons may participate in the improvement of behavioral performance in APP/PS1 mice after EE.
- Published
- 2019
20. A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells
- Author
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Xian-Dong Liu, Dong-Fu Feng, Li-Na He, Suya Sun, Tian-Le Xu, Jian Dong, Nan-Jie Xu, Xin-Rong Wu, and Yuan-Bo Pan
- Subjects
Physiological significance ,Neurogenesis ,Action Potentials ,Cell Communication ,Hippocampal formation ,Hippocampus ,Models, Biological ,Resting Phase, Cell Cycle ,Running ,Subgranular zone ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Neural Stem Cells ,medicine ,Animals ,Transcellular ,Research Articles ,Cells, Cultured ,030304 developmental biology ,Neurons ,Molecular switch ,0303 health sciences ,Multidisciplinary ,Cell cell contact ,Chemistry ,Kinase ,digestive, oral, and skin physiology ,SciAdv r-articles ,Cell Differentiation ,Cell Biology ,Neural stem cell ,Cell biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Dentate Gyrus ,Biomarkers ,030217 neurology & neurosurgery ,Research Article ,Neuroscience ,Signal Transduction - Abstract
Excitatory hippocampal granule cells regulate activation and transition of quiescent neural stem cells during voluntary exercise., The quiescence of radial neural stem cells (rNSCs) in adult brain is regulated by environmental stimuli. However, little is known about how the neurogenic niche couples the external signal to regulate activation and transition of quiescent rNSCs. Here, we reveal that long-term excitation of hippocampal dentate granule cells (GCs) upon voluntary running leads to activation of adult rNSCs in the subgranular zone and thereby generation of newborn neurons. Unexpectedly, the role of these excited GC neurons in NSCs depends on direct GC-rNSC interaction in the local niche, which is through down-regulated ephrin-B3, a GC membrane–bound ligand, and attenuated transcellular EphB2 kinase–dependent signaling in the adjacent rNSCs. Furthermore, constitutively active EphB2 kinase sustains the quiescence of rNSCs during running. These findings thus elucidate the physiological significance of GC excitability on adult rNSCs under external environments and indicate a key-lock switch regulation via cell-cell contact for functional transition of rNSCs.
- Published
- 2019
21. Fear extinction requires ASIC1a-dependent regulation of hippocampal-prefrontal correlates
- Author
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Xing Lei Song, Tian Le Xu, Michael X. Zhu, Ying Li, Qin Wang, Siyu Zhang, Qi Wang, Ti-Fei Yuan, Yan Jiao Wu, Wei Guang Li, Nan-Jie Xu, and Qin Jiang
- Subjects
0301 basic medicine ,Male ,Regulator ,Hippocampus ,Prefrontal Cortex ,Biology ,Hippocampal formation ,Extinction, Psychological ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neurotrophic factors ,Memory ,Conditioning, Psychological ,medicine ,Basic Helix-Loop-Helix Transcription Factors ,Animals ,Prefrontal cortex ,Research Articles ,Regulation of gene expression ,Mice, Knockout ,Neurons ,Multidisciplinary ,Brain-Derived Neurotrophic Factor ,SciAdv r-articles ,Life Sciences ,social sciences ,Extinction (psychology) ,Fear ,humanities ,Acid Sensing Ion Channels ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Gene Expression Regulation ,Neuroscience ,030217 neurology & neurosurgery ,Basolateral amygdala ,Research Article - Abstract
Learning to extinguish traumatic memory depends on fine-tuning of hippocampal-prefrontal connections via the ASIC1a channel., Extinction of conditioned fear necessitates the dynamic involvement of hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA), but key molecular players that regulate these circuits to achieve fear extinction remain largely unknown. Here, we report that acid-sensing ion channel 1a (ASIC1a) is a crucial molecular regulator of fear extinction, and that this function requires ASIC1a in ventral hippocampus (vHPC), but not dorsal hippocampus, mPFC, or BLA. While genetic disruption or pharmacological inhibition of ASIC1a in vHPC attenuated the extinction of conditioned fear, overexpression of the channel in this area promoted fear extinction. Channelrhodopsin-2–assisted circuit mapping revealed that fear extinction involved an ASIC1a-dependent modification of the long-range hippocampal-prefrontal correlates in a projection-specific manner. Gene expression profiling analysis and validating experiments identified several neuronal activity–regulated and memory-related genes, including Fos, Npas4, and Bdnf, as the potential mediators of ASIC1a regulation of fear extinction. Mechanistically, genetic overexpression of brain-derived neurotrophic factor (BDNF) in vHPC or supplement of BDNF protein in mPFC both rescued the deficiency in fear extinction and the deficits on extinction-driven adaptations of hippocampal-prefrontal correlates caused by the Asic1a gene inactivation in vHPC. Together, these results establish ASIC1a as a critical constituent in fear extinction circuits and thus a promising target for managing adaptive behaviors.
- Published
- 2018
22. Retrograde regulation of mossy fiber axon targeting and terminal maturation via postsynaptic Lnx1
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Nan-Jie Xu, Xian Dong Liu, Xiao Na Zhu, Tian Le Xu, Mark Henkemeyer, and Michael M. Halford
- Subjects
0301 basic medicine ,Mossy fiber (hippocampus) ,Receptor, EphB1 ,Receptor, EphB2 ,Ubiquitin-Protein Ligases ,PDZ domain ,Synaptogenesis ,Presynaptic Terminals ,Hippocampal formation ,Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Postsynaptic potential ,medicine ,Biological neural network ,Animals ,Axon ,Research Articles ,Mice, Knockout ,Pyramidal Cells ,Cell Biology ,CA3 Region, Hippocampal ,Axons ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Mossy Fibers, Hippocampal ,Synapses ,NUMB ,030217 neurology & neurosurgery - Abstract
Synapse formation relies on the coordination of dynamic pre- and postsynaptic structures during brain development. Liu et al. reveal that presynaptic terminal maturation of mossy fiber axons is retrogradely regulated by postsynaptic scaffold protein Lnx1 via stabilizing EphB receptor kinases., Neuronal connections are initiated by axon targeting to form synapses. However, how the maturation of axon terminals is modulated through interacting with postsynaptic elements remains elusive. In this study, we find that ligand of Numb protein X 1 (Lnx1), a postsynaptic PDZ protein expressed in hippocampal CA3 pyramidal neurons, is essential for mossy fiber (MF) axon targeting during the postnatal period. Lnx1 deletion causes defective synaptic arrangement that leads to aberrant presynaptic terminals. We further identify EphB receptors as novel Lnx1-binding proteins to form a multiprotein complex that is stabilized on the CA3 neuron membrane through preventing proteasome activity. EphB1 and EphB2 are independently required to transduce distinct signals controlling MF pruning and targeting for precise DG-CA3 synapse formation. Furthermore, constitutively active EphB2 kinase rescues structure of the wired MF terminals in Lnx1 mutant mice. Our data thus define a retrograde trans-synaptic regulation required for integration of post- and presynaptic structure that participates in building hippocampal neural circuits during the adolescence period., Graphical Abstract
- Published
- 2018
23. Gefitinib-Integrated Regimen versus Chemotherapy Alone in Heavily Pretreated Patients with Epidermal Growth Factor Receptor–Mutated Lung Adenocarcinoma: A Case-Control Study
- Author
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Ying-yi Wang, Ning Jia, Zhao Sun, Yu-zhou Wang, Xiaohong Ning, Nan-Jie Zhao, and Changting Meng
- Subjects
Oncology ,Chemotherapy ,medicine.medical_specialty ,Cancer Research ,biology ,business.industry ,medicine.medical_treatment ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Article ,Surgery ,Regimen ,Gefitinib ,Tolerability ,Internal medicine ,medicine ,biology.protein ,Adenocarcinoma ,Epidermal growth factor receptor ,business ,Prospective cohort study ,Survival rate ,medicine.drug - Abstract
BACKGROUND: The study aimed to compare the tolerability and efficacy of gefitinib combined with chemotherapy agents versus chemotherapy alone for the treatment of epidermal growth factor receptor (EGFR)–mutated lung adenocarcinoma in heavily pretreated patients. METHODS: The study was designed as a matched-pair case-control investigation to minimize intergroup heterogeneity. Patients were stratified into gefitinib plus chemotherapy and chemotherapy alone groups with matching for sex, age, ECOG performance status, progress-free survival (PFS) from previous EGFR tyrosine kinase inhibitor treatment, EGFR mutation types, and tumor metastasis status. RESULTS: Sixty-six patients were selected from our database using the matched-pair method. The median age was 61 years (95% confidence interval, 57-65 years). During a follow-up period of 14.5 months on average, the overall response rates of the gefitinib-integrated and chemotherapy alone groups were 9.1% and 6.5%, respectively (P > .05), whereas the corresponding disease-control rates were 39.4% and 30.3%, respectively (P > .05). No statistically significant differences in PFS (median, 4.2 vs 3.3 months; P = .06) and overall survival (median, 10.4 vs 7.9 months; P = .44) were observed between two groups. The 6-month survival rates of the gefitinib-integrated and chemotherapy alone groups were 21.2% and 12.1%, respectively (P < .05). Side effects were mild, and all treatments were well tolerated. CONCLUSIONS: Our results indicated that gefitinib-integrated therapy offered a trend to better PFS and an improved 6-month survival rate in heavily pretreated patients with metastatic EGFR-mutated lung adenocarcinoma. All treatments were well tolerated. Future prospective studies are warranted to confirm our findings.
- Published
- 2014
24. Microstructural brain abnormalities of children of idiopathic generalized epilepsy with generalized tonic-clonic seizure: A voxel-based diffusional kurtosis imaging study
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He Wang, Bangxian Wu, Junling Gao, Minhua Lu, Po-Man Wu, Bingsheng Huang, Xiaoming He, Nan-Jie Gong, and Shi-Ting Feng
- Subjects
Generalized tonic-clonic seizure ,business.industry ,Imaging study ,medicine.disease ,computer.software_genre ,Idiopathic generalized epilepsy ,Voxel ,medicine ,Kurtosis ,Journal editor ,Radiology, Nuclear Medicine and imaging ,Nuclear medicine ,business ,computer - Abstract
The above article, published online on 3 May 2014 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, and Wiley Periodicals, Inc. The retraction has been agreed due to errors in the results of the published article. The authors stated in the Methods section that ‘. . . only clusters with a false discovery rate (FDR)-corrected P-value less than 0.05 were included.’ However, it was subsequently discovered that the FDG-correction had not been performed correctly. Had this been carried out in the right way, the difference between the case group and the control group in most of the presented regions would have been insignificant. REFERENCE 1. Gao J, Feng S-T, Wu B, Gong N, Lu M, Wu P-M, Wang H, He X, and Huang B. Microstructural Brain Abnormalities of Children of Idiopathic Generalized Epilepsy With Generalized Tonic-Clonic Seizure: A Voxel-Based Diffusional Kurtosis Imaging Study J mag res. 2014 May 3. doi: 10.1002/jmri.24647 [epub ahead of print]
- Published
- 2014
25. Prevalence of synchronous second primary malignancy: identification using whole body PET/CT imaging
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Gong Nan-Jie, Chu Yiu-Ching, and Wong Chun-Sing
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Male ,medicine.medical_specialty ,Whole body imaging ,Malignancy ,Multimodal Imaging ,Metastasis ,Benign tumor ,Fluorodeoxyglucose F18 ,Neoplasms ,Prevalence ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Aged, 80 and over ,PET-CT ,business.industry ,Neoplasms, Second Primary ,Second primary cancer ,Middle Aged ,medicine.disease ,Positron-Emission Tomography ,Radiological weapon ,Female ,Whole body pet ,Radiology ,Tomography, X-Ray Computed ,Nuclear medicine ,business - Abstract
Objective To describe the prevalence of synchronous second primary malignancy detected by PET/ CT in our clinical practice and its differentiating features from metastatic lesion. Methods All PET/CT scans from 1st October 2009 to 30th September 2010 were reviewed. The suspected cases of synchronous second primary malignancy detected by PET/CT were selected, and the histologically confirmed ones were being illustrated. Metachronous second primary cases were excluded. Results A total of 1522 scans were reviewed. sixty-eight cases were suspected to have a synchronous second primary while 8 were histologically confirmed. Seven (0.4%) of them were malignant and 1 was a benign tumor. These 7 cases were illustrated, and we found a significant difference in SUVmax values and site of occurrence unusual to metastasis that were the two main radiological features differentiating them from metastatic lesion. Conclusion Synchronous second primary malignancy could be missed without the use of whole body imaging. Its diagnosis is of utmost importance to prevent erroneous upstaging of disease and subsequent palliative treatment instead of curative surgery.
- Published
- 2014
26. Tumor Volumes Measured From Static and Dynamic 18F-fluoro-2-deoxy-D-glucose Positron Emission Tomography-Computed Tomography Scan
- Author
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Jan Axelsson, Shi-Ting Feng, Junling Gao, Liangping Luo, Jinzhao Jiang, Nan-Jie Gong, Hanwei Chen, Minyi Cui, Dan Liu, and Bingsheng Huang
- Subjects
Adult ,Male ,genetic structures ,Quantitative Biology::Tissues and Organs ,Tumor burden ,Contrast Media ,Multimodal Imaging ,Quantitative Biology::Cell Behavior ,chemistry.chemical_compound ,Nuclear magnetic resonance ,Fluorodeoxyglucose F18 ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Positron Emission Tomography-Computed Tomography ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Primary tumor ,Iopamidol ,Tumor Burden ,chemistry ,Head and Neck Neoplasms ,Positron emission tomography ,Positron-Emission Tomography ,Female ,Tomography ,Radiopharmaceuticals ,CRITERION STANDARD ,Tomography, X-Ray Computed ,2-Deoxy-D-glucose ,Nuclear medicine ,business - Abstract
The objective of this study was to compare the accuracy of calculating the primary tumor volumes using a gradient-based method and fixed threshold methods on the standardized uptake value (SUV) maps and the net influx of FDG (Ki) maps from positron emission tomography-computed tomography (PET-CT) images.Newly diagnosed patients with head and neck cancer were recruited, and dynamic PET-CT scan and T2-weighted magnetic resonance imaging were performed. The maps of Ki and SUV were calculated from PET-CT images. The tumor volumes were calculated using a gradient-based method and a fixed threshold method at 40% of maximal SUV or maximal Ki. Four kinds of volumes, VOLKi-Gra (from the Ki maps using the gradient-based method), VOLKi-40% (from the Ki maps using the threshold of 40% maximal Ki), VOLSUV-Gra (from the SUV maps using the gradient-based method), and VOLSUV-40% (from the SUV maps using the threshold of 40% maximal SUV), were acquired and compared with VOLMRI (the volumes acquired on T2-weighted images) using the Pearson correlation, paired t test, and similarity analysis.Eighteen patients were studied, of which 4 had poorly defined tumors (PDT). The positron emission tomography-derived volumes were as follows: VOLSUV-40%, 2.1 to 41.2 cm (mean [SD], 12.3 [10.6]); VOLSUV-Gra, 2.2 to 28.1 cm (mean [SD], 13.2 [8.4]); VOLKi-Gra, 2.4 to 17.0 cm (mean [SD], 9.5 [4.6]); and VOLKi-40%, 2.7 to 20.3 cm (mean [SD], 12.0 [6.0]). The VOLMRI ranged from 2.9 to 18.1 cm (mean [SD], 9.1 [3.9]). The VOLKi-Gra significantly correlated with VOLMRI with the highest correlation coefficient (PDT included, R = 0.673, P = 0.002; PDT excluded, R = 0.841, P0.001) and presented no difference from VOLMRI (P = 0.672 or 0.561, respectively, PDT included and excluded). The difference between VOLKi-Gra and VOLMRI was also the smallest.The tumor volumes delineated on the Ki maps using the gradient-based method are more accurate than those on the SUV maps and using the fixed threshold methods.
- Published
- 2014
27. Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study
- Author
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Yiu-Ching Chu, Lam-Ming Leung, Chun-Sing Wong, Nan-Jie Gong, and Chun-Chung Chan
- Subjects
Male ,medicine.medical_specialty ,Biomedical Engineering ,Biophysics ,Audiology ,Nerve Fibers, Myelinated ,Sensitivity and Specificity ,Severity of Illness Index ,White matter ,Correlation ,Alzheimer Disease ,Image Interpretation, Computer-Assisted ,Fractional anisotropy ,Severity of illness ,Humans ,Medicine ,Cognitive Dysfunction ,Radiology, Nuclear Medicine and imaging ,Aged ,Neurons ,business.industry ,Reproducibility of Results ,Cognition ,Image Enhancement ,Diffusion Magnetic Resonance Imaging ,medicine.anatomical_structure ,Kurtosis ,Mann–Whitney U test ,Female ,business ,Algorithms ,Diffusion MRI - Abstract
Object Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency. Materials and Methods DKI was performed on 18 AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann–Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation. Results In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM. Conclusion Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM.
- Published
- 2013
28. Imaging biomarker with T1ρ and T2 mappings in osteoarthritis – In vivo human articular cartilage study
- Author
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Chun-Sing Wong, Chun Hoi Yan, Teng Li, Queenie Chan, Yiu Ching Chu, and Nan-Jie Gong
- Subjects
Cartilage, Articular ,Male ,Pathology ,medicine.medical_specialty ,Treatment response ,Imaging biomarker ,Articular cartilage ,Osteoarthritis ,In vivo ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Stage (cooking) ,Arthroplasty, Replacement, Knee ,Aged ,Glycosaminoglycans ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Cartilage ,Magnetic resonance imaging ,General Medicine ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Female ,business ,Biomarkers - Abstract
Introduction Osteoarthritis (OA) of the knee is a common and disabling disease worldwide. Its prevalence is increasing in view of the aging population. Changes in collagen content, its orientation and GAG content in the articular cartilage with age are the major features in knee osteoarthritis. These changes in collagen and GAG contents show no manifestation in plain radiography and conventional magnetic resonance imaging (MRI). Nevertheless, early diagnosis of the knee osteoarthritis is of paramount importance clinically in view of the evolution of putative interventions in its early stage. The aim of this project is to identify the relationships between the two imaging biomarkers (i.e. T1ρ and T2 mappings) and the GAG concentration in living human symptomatic cartilage. Methodology 28 patients with clinical diagnosis of knee osteoarthritis were enrolled. 7 males and 16 females were recruited and their mean age was 68.1 (ranges from 53 to 84). Conventional PD sequence, T1ρ and T2 mappings were performed for each subject within 1 week before total knee arthroplasty. Articular cartilage from the lateral tibial plateau was harvested and the GAG content in cartilage was determined by using dimethylmethylene blue method. T1ρ mean and T2 values were calculated and correlate with GAG concentration statistically. Results The mean value T1ρ was 40.3 ± 13.5 ms, ranging from 15.3 to 69.3 ms and the mean value T2 was 31.0 ± 10.5 ms, ranging from 16.1 to 46.9 ms. The mean value of GAG content was 80.1 ± 33.3 mg, ranging from 24.9 to 166.0 mg while the mean value of GAG concentration was 267.4 ± 165.9 mg/cm3, ranging from 91.3 to 760.5 mg/cm3. T2 values were inversely correlated with GAG concentration with R2 = 0.375, p = 0.001 while T1ρ values were also inversely correlated with GAG concentration with R2 = 0.200, p = 0.025. Conclusion This in vivo study confirmed that T1ρ and T2 values correlate with the GAG concentration in living human knee cartilages which corroborate with the previous works. The later (T2 values) is found more reliable in our study and less controversial in literatures. We postulate that T2 values can serve as a non-invasive imaging biomarker in the progress of knee osteoarthritis in terms of both disease diagnosis and treatment response monitoring.
- Published
- 2013
29. Amygdala EphB2 Signaling Regulates Glutamatergic Neuron Maturation and Innate Fear
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Xiao Na Zhu, Hanyi Zhuang, Jingyu Yang, Xian Dong Liu, Nan-Jie Xu, and Mark Henkemeyer
- Subjects
0301 basic medicine ,Aging ,Receptor, EphB2 ,Neurogenesis ,Mice, Transgenic ,Amygdala ,Synapse ,03 medical and health sciences ,Glutamatergic ,Mice ,0302 clinical medicine ,Glutamates ,medicine ,Animals ,Ephrin B3 ,Defense Mechanisms ,Fear processing in the brain ,Instinct ,Mice, Knockout ,Neurons ,General Neuroscience ,Gene Expression Regulation, Developmental ,Fear ,Articles ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Neuron maturation ,Neuron ,Psychology ,Neuroscience ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
The amygdala serves as emotional center to mediate innate fear behaviors that are reflected through neuronal responses to environmental aversive cues. However, the molecular mechanism underlying the initial neuron responses is poorly understood. In this study, we monitored the innate defensive responses to aversive stimuli of either elevated plus maze or predator odor in juvenile mice and found that glutamatergic neurons were activated in amygdala. Loss of EphB2, a receptor tyrosine kinase expressed in amygdala neurons, suppressed the reactions and led to defects in spine morphogenesis and fear behaviors. We further found a coupling of spinogenesis with these threat cues induced neuron activation in developing amygdala that was controlled by EphB2. A constitutively active form of EphB2 was sufficient to rescue the behavioral and morphological defects caused by ablation of ephrin-B3, a brain-enriched ligand to EphB2. These data suggest that kinase-dependent EphB2 intracellular signaling plays a major role for innate fear responses during the critical developing period, in which spinogenesis in amygdala glutamatergic neurons was involved.SIGNIFICANCE STATEMENTGeneration of innate fear responses to threat as an evolutionally conserved brain feature relies on development of functional neural circuit in amygdala, but the molecular mechanism remains largely unknown. We here identify that EphB2 receptor tyrosine kinase, which is specifically expressed in glutamatergic neurons, is required for the innate fear responses in the neonatal brain. We further reveal that EphB2 mediates coordination of spinogenesis and neuron activation in amygdala during the critical period for the innate fear. EphB2 catalytic activity plays a major role for the behavior upon EphB–ephrin-B3 binding and transnucleus neuronal connections. Our work thus indicates an essential synaptic molecular signaling within amygdala that controls synapse development and helps bring about innate fear emotions in the postnatal developing brain.
- Published
- 2016
30. Treatment response monitoring in patients with gastrointestinal stromal tumor using diffusion-weighted imaging: preliminary results in comparison with positron emission tomography/computed tomography
- Author
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Jing Gu, Yiu-Ching Chu, Chun-Sing Wong, and Nan-Jie Gong
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,Receiver operating characteristic ,GiST ,business.industry ,Standardized uptake value ,Lesion ,Positron emission tomography ,medicine ,Molecular Medicine ,Effective diffusion coefficient ,Radiology, Nuclear Medicine and imaging ,Radiology ,medicine.symptom ,Stromal tumor ,Nuclear medicine ,business ,Spectroscopy ,Diffusion MRI - Abstract
We compared the parameters derived from diffusion-weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) for treatment response evaluation and response prediction in patients with gastrointestinal stromal tumor (GIST). Seven patients with histologically proven metastatic disease were enrolled. DWI and PET/CT data were collected from all patients at diagnosis and from six at follow-up. All 37 lesions were identifiable in DWI with a sensitivity of 100%. To achieve higher accuracy, we used the apparent diffusion coefficient (ADC) of liver and background noise as thresholds for the measurement of the ADCs of lesions. Significant inverse correlations were found between ADCmean_thr (ADCmean with thresholds) and SUVmean (mean standardized uptake value) (R2 = 0.523, p
- Published
- 2012
31. Ephrin-B3 coordinates timed axon targeting and amygdala spinogenesis for innate fear behaviour
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Suya Sun, Xiao Na Zhu, Xian Dong Liu, Jingyu Yang, Mark Henkemeyer, Nan-Jie Xu, and Hanyi Zhuang
- Subjects
0301 basic medicine ,Time Factors ,Science ,Neurogenesis ,General Physics and Astronomy ,Ephrin-B3 ,Biology ,Amygdala ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Biological neural network ,Premovement neuronal activity ,Animals ,Ephrin B3 ,Axon ,Cell Nucleus ,Instinct ,Multidisciplinary ,General Chemistry ,Fear ,medicine.disease ,Axons ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Schizophrenia ,Mutation ,Synapses ,Autism ,Neuroscience ,psychological phenomena and processes ,030217 neurology & neurosurgery - Abstract
Innate emotion response to environmental stimuli is a fundamental brain function that is controlled by specific neural circuits. Dysfunction of early emotional circuits may lead to neurodevelopmental disorders such as autism and schizophrenia. However, how the functional circuits are formed to prime initial emotional behaviours remain elusive. We reveal here using gene-targeted mutations an essential role for ephrin-B3 ligand-like activity in the development of innate fear in the neonatal brain. We further demonstrate that ephrin-B3 controls axon targeting and coordinates spinogenesis and neuronal activity within the amygdala. The morphological and behavioural abnormalities in ephrin-B3 mutant mice are rescued by conditional knock-in of wild-type ephrin-B3 during the critical period when axon targeting and fear responses are initiated. Our results thus define a key axonal molecule that participates in the wiring of amygdala circuits and helps bring about fear emotion during the important adolescence period., The molecular mechanism underlying initial circuit wiring in amygdala is poorly understood. Here the authors show that ephrin-B3 is required for axon targeting and amygdala spinogenesis during a critical period in development, and plays an important role in amygdala mediated fear responses.
- Published
- 2015
32. Is Lymph Node Metastasis a Common Feature of Gastrointestinal Stromal Tumor?
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Nanjie, Gong, Gong Nan, Jie, Chun Sing, Wong, Wong Chun, Sing, Yiu Ching, Chu, Chu Yiu, Ching, and Tiffany
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Gastrointestinal Stromal Tumors ,Metastasis ,symbols.namesake ,Internal medicine ,Statistical significance ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Stromal tumor ,Child ,Lymph node ,Fisher's exact test ,Aged ,Retrospective Studies ,Aged, 80 and over ,PET-CT ,GiST ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Primary tumor ,medicine.anatomical_structure ,Lymphatic Metastasis ,Positron-Emission Tomography ,symbols ,Female ,Tomography, X-Ray Computed ,business - Abstract
Purpose: We investigated the incidence of lymph node metastasis in gastrointestinal stromal tumor (GIST) patients in our PET/CT database. The demographic data and characteristics of the primary tumor were evaluated in GIST patients with or without lymph node metastasis. Materials and Methods: We reviewed our PET/CT database from January 1, 2007 to November 30, 2010 by using keyword search, and identified GIST with lymph node metastasis according to our standard of reference. Statistical analysis was conducted between GIST group with or without lymph node metastasis based on the age, sex, primary tumor size, and primary tumor location. Results: A total of 29 GIST patients were found in our database. Six of them had lymph node metastasis, corresponding to 20.7%. When considering only the adult patients, the incidence was 17% (5 out of 28). There were 4 males and 1 female, with the mean age of 66.8 years old, which was 8 years older than the group without lymph node metastasis. Of the 5 adult metastasis patients, 4 had their primary tumor located at very rare sites other than stomach or small bowel. Statistical analysis using Fisher exact test of rare location showed significance between the 2 groups with P = 0.004. The mean size of the primary tumor in the group with lymph node metastasis was 5.2 cm, which was 2.9 cm less than the group without metastasis. No statistical significance was found in age, sex, or size of primary tumor between the 2 groups. Conclusion: The incidence of lymph node metastasis in GISTs in our database is 20.7%, which is surprisingly higher than we thought from other previous studies. In contrast to the group without lymph node metastasis, these patients tend to be of older ages and had rare location of the primary tumor. This result supports further study with larger sample size.
- Published
- 2011
33. Ephrin-B3 reverse signaling through Grb4 and cytoskeletal regulators mediates axon pruning
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Mark Henkemeyer and Nan-Jie Xu
- Subjects
Dock180 ,hippocampus ,Growth Cones ,Ephrin-B3 ,Mice, Transgenic ,macromolecular substances ,Biology ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Axon terminal ,Transduction, Genetic ,mossy fiber ,Chlorocebus aethiops ,medicine ,Animals ,NCK2 ,Ephrin ,Gene Knock-In Techniques ,Ephrin B3 ,Axon ,Cells, Cultured ,reverse signaling ,Adaptor Proteins, Signal Transducing ,030304 developmental biology ,Hippocampal mossy fiber ,Mice, Knockout ,Oncogene Proteins ,0303 health sciences ,axon guidance ,General Neuroscience ,tyrosine phosphorylation ,Actins ,Axons ,Coculture Techniques ,Cell biology ,Cytoskeletal Proteins ,medicine.anatomical_structure ,nervous system ,COS Cells ,Mossy Fibers, Hippocampal ,Axon guidance ,Neuroscience ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
It has been suggested that ephrin-B proteins have receptor-like roles in the control of axon pathfinding by repulsion, although it is largely unknown how the reverse signals are coupled to downstream intracellular molecules and how they induce cytoskeletal reorganization at the axon terminal. We found that ephrin-B3 (EB3) was able to function as a repulsive guidance receptor and mediate stereotyped pruning of murine hippocampal mossy fiber axons during postnatal development. Targeted intracellular point mutants showed that axon pruning requires tyrosine phosphorylation-dependent reverse signaling and coupling to the SH2/SH3 adaptor protein Grb4 (also known as Nckbeta/Nck2). Furthermore, we found that the second SH3 domain of Grb4 is required and sufficient for axon pruning/retraction by mediating interactions with Dock180 and PAK to bring about guanine nucleotide exchange and signaling downstream of Rac, respectively. Our results reveal a previously unknown pathway that controls axon pruning and elucidate the biochemical mechanism by which ephrin-B reverse signals regulate actin dynamics to bring about the retraction of growth cones.
- Published
- 2009
34. Morphine modulates glutamate release in the hippocampal CA1 area in mice
- Author
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Chunfu Wu, Gang Pei, Nan-Jie Xu, Yuting Li, Jingyu Yang, and Ming Guo
- Subjects
Male ,medicine.medical_specialty ,Central nervous system ,Glutamic Acid ,Hippocampus ,Hippocampal formation ,Biology ,Synaptic Transmission ,Mice ,chemistry.chemical_compound ,Glutamatergic ,Internal medicine ,medicine ,Animals ,Neurotransmitter ,Dose-Response Relationship, Drug ,Morphine ,General Neuroscience ,Glutamate receptor ,Adaptation, Physiological ,Substance Withdrawal Syndrome ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,nervous system ,chemistry ,Opiate ,Morphine Dependence ,medicine.drug - Abstract
Opiate abuse is associated with long-lasting neural adaptative changes in the brain. Increasing evidence demonstrates that opiates significantly alter the function of the glutamatergic system, while how the system is regulated still remains elusive. In the present study, we studied the effect of morphine on extracellular glutamate concentration in the hippocampus, a nucleus rich of the glutamatergic neurons. The results showed that glutamate concentration in the extracellular fluid of the hippocampus was decreased following either acute or chronic treatment of morphine. However, naloxone-induced withdrawal increased glutamate concentration significantly. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine treatment.
- Published
- 2005
35. Spatial learning and morphine-rewarded place preference negatively correlates in mice
- Author
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Ling-Zhi Wang, Gang Pei, Nan-Jie Xu, and Chunfu Wu
- Subjects
Male ,Narcotics ,medicine.medical_specialty ,Clinical Biochemistry ,Morris water navigation task ,Toxicology ,Biochemistry ,Developmental psychology ,Mice ,Behavioral Neuroscience ,Reward ,Internal medicine ,medicine ,Animals ,Maze Learning ,Biological Psychiatry ,Pharmacology ,Mice, Inbred ICR ,Morphine ,Spontaneous alternation ,Preference ,Conditioned place preference ,Endocrinology ,Spatial learning ,Conditioning, Operant ,Conditioning ,Opiate ,Psychology ,psychological phenomena and processes ,medicine.drug - Abstract
Accumulating evidence has indicated that there might exist some correlation between opiate reward and certain kinds of learning and memory processes. The present study attempted to investigate the correlation between individual differences in morphine reward and capacities in spatial learning and spontaneous alternation. In the present studies, good-response (GR) and poor-response (PR) mice were respectively selected according to their performance in a spatial learning test involving the Morris water maze or in a spontaneous alternation task using the Y-maze. In a place preference conditioning procedure, morphine (3.0 mg/kg) produced significant conditioned place preference (CPP) in both GR and PR mice selected by using either the Morris water maze or the Y-maze. The PR mice selected with the Morris water maze showed significantly more CPP induced by morphine than the GR mice. However, no detectable difference was observed in morphine-induced CPP between the GR and PR mice selected with the Y-maze. These results suggested that the variation in morphine-induced CPP in mice is somehow differentially related to that of spatial learning but unlikely to that of spontaneous alternation.
- Published
- 2001
36. Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging
- Author
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Chun-Chung Chan, Nan-Jie Gong, Chun-Sing Wong, Yiu-Ching Chu, and Lam-Ming Leung
- Subjects
Adult ,Male ,Aging ,Internal capsule ,Caudate nucleus ,Corpus callosum ,White matter ,Nuclear magnetic resonance ,Cognition ,Fractional anisotropy ,medicine ,Humans ,Gray Matter ,Aged ,Aged, 80 and over ,General Neuroscience ,Putamen ,Middle Aged ,White Matter ,medicine.anatomical_structure ,Globus pallidus ,Diffusion Magnetic Resonance Imaging ,nervous system ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Psychology ,Neuroscience ,Developmental Biology ,Diffusion MRI - Abstract
Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations.
- Published
- 2013
37. IC‐P‐149: Axonal loss or demyelination? Decreased integrity of white matter tracts revealed by diffusional kurtosis imaging in Alzheimer's disease and mild cognitive impairment
- Author
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Chun-Sing Wong, Nan-Jie Gong, Lam-Ming Leung, and Chun-Chung Chan
- Subjects
Epidemiology ,business.industry ,Health Policy ,Axonal loss ,Disease ,White matter ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Developmental Neuroscience ,medicine ,Kurtosis ,Neurology (clinical) ,Geriatrics and Gerontology ,Cognitive impairment ,business ,Neuroscience - Published
- 2013
38. IC‐P‐148: Age‐related microstructural alterations in deep gray matter: In vivo evidence from diffusional kurtosis imaging
- Author
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Nan-Jie Gong, Lam-Ming Leung, Chun-Sing Wong, and Chun-Chung Chan
- Subjects
education.field_of_study ,Epidemiology ,Chemistry ,Health Policy ,Population ,Partial volume ,medicine.disease ,computer.software_genre ,White matter ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Nuclear magnetic resonance ,Atrophy ,Developmental Neuroscience ,Voxel ,medicine ,Arcuate fasciculus ,Neurology (clinical) ,Geriatrics and Gerontology ,education ,computer ,Diffusion MRI ,Tractography - Abstract
[1] to compare 46 AD patients with 94 age-matched healthy volunteers (Australian Imaging Biomarkers & Lifestyle study). AFD is proportional to the image intensity, which is related to the quantity of intra-axonal water, and is therefore sensitive to the number of axons within a voxel (density). To perform voxel-wise comparisons of AFD, images were non-linearly warped to a common template image. We incorporated morphology information by modulating the AFD in each voxel based on the change to a fibre bundle’s cross-sectional area (atrophy). Modulation ensures the AFD in template space encapsulates both sources of axonal loss (axon density as measured by the MRI signal, and volume loss due to atrophy). We investigated whole-brain group AFD differences with and without modulation using novel tractography-based statistics. Results: Significant AFD decreases in AD were observed in white matter bundles known to be involved in language and memory (Fig.1). As shown in columns 1 & 2, the group AFD difference is more extensive when morphology information is included via AFDmodulation. Since AFD differences are associated with a voxel and direction (shown by the direction-colour-encoded tractogram in Fig.1) population differences can be attributed to a specific fibre bundle in regions with crossing-fibres (e.g. Arcuate Fasciculus).The absence of differences in fibre density (column 1) within regions previously detected using FA suggests that FA decreases detected in AD are largely caused by atrophy-induced partial volume changes. Conclusions: By incorporating morphology information, AFD is potentially a more sensitive and interpretable biomarker of axon degeneration compared to existing diffusion MRI measures based on image intensity alone.[1] Raffelt et al.2012,59(4):3976-94.
- Published
- 2013
39. Increasing the accuracy of volume and ADC delineation for heterogeneous tumor on diffusion-weighted MRI: correlation with PET/CT
- Author
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Yiu-Ching Chu, Chun-Sing Wong, Hua Guo, Bingsheng Huang, Nan-Jie Gong, and Queenie Chan
- Subjects
Cancer Research ,Gastrointestinal Stromal Tumors ,Standardized uptake value ,Multimodal Imaging ,Fluorodeoxyglucose F18 ,medicine ,Image Processing, Computer-Assisted ,Effective diffusion coefficient ,Humans ,Radiology, Nuclear Medicine and imaging ,Retrospective Studies ,PET-CT ,Radiation ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Middle Aged ,Thresholding ,Tumor Burden ,body regions ,Diffusion Magnetic Resonance Imaging ,Oncology ,Positron emission tomography ,Positron-Emission Tomography ,Linear Models ,Tomography ,Radiopharmaceuticals ,Nuclear medicine ,business ,Tomography, X-Ray Computed ,Algorithms ,Diffusion MRI - Abstract
To improve the accuracy of volume and apparent diffusion coefficient (ADC) measurements in diffusion-weighted magnetic resonance imaging (MRI), we proposed a method based on thresholding both the b0 images and the ADC maps.In 21 heterogeneous lesions from patients with metastatic gastrointestinal stromal tumors (GIST), gross lesion were manually contoured, and corresponding volumes and ADCs were denoted as gross tumor volume (GTV) and gross ADC (ADC(g)), respectively. Using a k-means clustering algorithm, the probable high-cellularity tumor tissues were selected based on b0 images and ADC maps. ADC and volume of the tissues selected using the proposed method were denoted as thresholded ADC (ADC(thr)) and high-cellularity tumor volume (HCTV), respectively. The metabolic tumor volume (MTV) in positron emission tomography (PET)/computed tomography (CT) was measured using 40% maximum standard uptake value (SUV(max)) as the lower threshold, and corresponding mean SUV (SUV(mean)) was also measured.HCTV had excellent concordance with MTV according to Pearson's correlation (r=0.984, P.001) and linear regression (slope = 1.085, intercept = -4.731). In contrast, GTV overestimated the volume and differed significantly from MTV (P=.005). ADC(thr) correlated significantly and strongly with SUV(mean) (r=-0.807, P.001) and SUV(max) (r=-0.843, P.001); both were stronger than those of ADC(g).The proposed lesion-adaptive semiautomatic method can help segment high-cellularity tissues that match hypermetabolic tissues in PET/CT and enables more accurate volume and ADC delineation on diffusion-weighted MR images of GIST.
- Published
- 2013
40. Roles of Ginsenosides on Morphine-Induced Hyperactivity and Rewarding Effect in Mice
- Author
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Jin-Hui Wang, Jingyu Yang, Xian Li, Ming Guo, Dan Zhu, Nan-Jie Xu, Chunfu Wu, and Gang Pei
- Subjects
Male ,Ginsenosides ,Ratón ,Panax ,Pharmaceutical Science ,Motor Activity ,Pharmacognosy ,Pharmacology ,Plant Roots ,Analytical Chemistry ,Mice ,chemistry.chemical_compound ,Ginseng ,Drug Discovery ,Animals ,Medicine ,Morphine ,biology ,business.industry ,Organic Chemistry ,Biological activity ,biology.organism_classification ,Conditioned place preference ,Complementary and alternative medicine ,chemistry ,Ginsenoside ,Molecular Medicine ,Araliaceae ,business ,Phytotherapy ,medicine.drug - Abstract
Ginsenosides, the main effective components of the root of Panax ginseng, have been reported to modulate morphine action. In the present study, ginsenosides Rd, Rb2, Rg1 and Re were divided into two groups according to their effects in mice on morphine-induced hyperactivity and conditioned place preference (CPP). Ginsenosides Rd, Rb2, Rg1 had no effect on morphine-induced hyperactivity, but antagonized morphine-induced CPP. On the contrary, ginsenoside Re increased morphine-induced hyperactivity whereas it showed no effect on morphine-induced CPP. Furthermore, Re antagonized the inhibitory effect of the mixture involving Rd, Rb2 and Rg1 on the morphine action. These results suggest that ginsenosides with different structures have antagonizing properties in the regulation of morphine-induced reinforcement.
- Published
- 2004
41. Inhibition of Activity of GABA Transporter GAT1 by δ-Opioid Receptor
- Author
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Thomas Fucke, Nan-Jie Xu, Wolfgang Schwarz, Peng Xia, Gang Pei, Lu Pu, Quanbao Gu, and Shuanglai Ren
- Subjects
Neurotransmitter transporter ,Article Subject ,biology ,business.industry ,medicine.drug_class ,lcsh:Other systems of medicine ,Pharmacology ,lcsh:RZ201-999 ,Inhibitory postsynaptic potential ,Periaqueductal gray ,gamma-Aminobutyric acid ,Complementary and alternative medicine ,Opioid receptor ,ddc:570 ,biology.protein ,Medicine and Health Sciences ,GABAergic ,Medicine ,GABA transporter ,ddc:610 ,business ,Research Article ,Dopamine transporter ,medicine.drug - Abstract
Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR) activation. Here we investigated regulation of GABA transporter GAT1 byδOR in rats and inXenopusoocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouseδOR andμOR inXenopusoocytes. The function of GAT1 was analyzed in terms of Na+-dependent [3H]GABA uptake as well as GAT1-mediated currents. Coexpression ofδOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation ofδOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression ofμOR, as well asμOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation ofδOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia.
- Published
- 2012
42. Ephrin reverse signaling in axon guidance and synaptogenesis
- Author
-
Mark Henkemeyer and Nan-Jie Xu
- Subjects
Dendritic spike ,Synaptogenesis ,Intracellular Signaling Peptides and Proteins ,Brain ,Dendrite ,Cell Biology ,Dendrites ,Biology ,biological factors ,Article ,Axons ,Cell biology ,medicine.anatomical_structure ,nervous system ,Synapses ,medicine ,Biological neural network ,Ephrin ,Animals ,Axon guidance ,Neuron ,Axon ,Ephrins ,Developmental Biology ,Signal Transduction - Abstract
Axon-cell and axon-dendrite contact is a highly regulated process necessary for the formation of precise neural circuits and a functional neural network. Eph-ephrin interacting molecules on the membranes of axon nerve terminals and target dendrites act as bidirectional ligands/receptors to transduce signals into both the Eph-expressing and ephrin-expressing cells to regulate cytoskeletal dynamics. In particular, recent evidence indicates that ephrin reverse signal transduction events are important in controlling both axonal and dendritic elaborations of neurons in the developing nervous system. Here we review how ephrin reverse signals are transduced into neurons to control maturation of axonal pre-synaptic and dendritic post-synaptic structures.
- Published
- 2011
43. Correlation of measurements from diffusion weighted MR imaging and FDG PET/CT in GIST patients: ADC versus SUV
- Author
-
Nan-Jie Gong, Pek-Lan Khong, Marina-Portia Anthony, Ho Fun Lee, Chun-Sing Wong, Kent man Chu, Yiu-Ching Chu, and Queenie Chan
- Subjects
Male ,medicine.medical_specialty ,Gastrointestinal Stromal Tumors ,Statistics as Topic ,Multimodal Imaging ,Sensitivity and Specificity ,Correlation ,Lesion ,Fluorodeoxyglucose F18 ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Diffusion-Weighted MR Imaging ,Gastrointestinal Neoplasms ,PET-CT ,medicine.diagnostic_test ,GiST ,business.industry ,Reproducibility of Results ,General Medicine ,Middle Aged ,body regions ,Diffusion Magnetic Resonance Imaging ,Positron emission tomography ,Positron-Emission Tomography ,Fdg pet ct ,Female ,Tomography ,Radiology ,medicine.symptom ,Radiopharmaceuticals ,business ,Nuclear medicine ,Tomography, X-Ray Computed - Abstract
Purpose We investigated the correlation relationship between ADCs measured by MRI and SUVs measured by PET/CT of lesions on GIST (gastrointestinal stromal tumor) patients to verify if MR is able to replace or serve as an alternative to PET/CT in GIST staging and treatment monitoring. Materials and methods Between September 2010 and January 2011, five patients with histologically proven metastatic GIST in Queen Mary Hospital, Hong Kong were enrolled into our study. All patients underwent both MRI and PET/CT scans at prognosis. Pearson's correlations of twenty-nine lesions were conducted between 5 pairs of ADCs and SUVs values. Results Lesions in the liver, peritoneum or bowel loops were found by PET/CT and no extra-abdominal lesion was identified. All twenty-nine lesions are identifiable by MRI with sensitivity of 100%. Significant inverse correlation were found between ADC mean and SUV mean ( P = 0.006), ADC mean and SUV max ( P = 0.010), ADC min and SUV max ( P = 0.014), ADC min and SUV mean ( P = 0.026), rADC min and rSUV max ( P = 0.047). Conclusion DWI is comparable to PET/CT in visually detecting the GIST lesions’ location. Significant inverse correlations were found between ADCs from DWIBS and SUVs from PET/CT on data of GIST patients. This finding demonstrates that DWI is potentially capable of offering similar information for diagnosis and treatment response evaluating in GIST's patients as PET/CT does. Furthermore, ADC min , which is determined by single pixel, is not as reliable as ADC mean , which is weighted average value of the whole lesion volume.
- Published
- 2011
44. Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction
- Author
-
Wenliang Lei, Jia Wang, Fei Chen, Nan-jie Ruan, Lei Qian, and Zhen-Ge Luo
- Subjects
animal structures ,Beta-catenin ,Neuromuscular Junction ,Muscle Proteins ,Biochemistry ,Neuromuscular junction ,Cell Line ,Mice ,Postsynaptic potential ,medicine ,Animals ,Cluster Analysis ,Receptors, Cholinergic ,Promoter Regions, Genetic ,Molecular Biology ,beta Catenin ,Acetylcholine receptor ,biology ,Myogenesis ,Muscles ,Wnt signaling pathway ,Cell Differentiation ,Cell Biology ,Cell biology ,body regions ,Wnt Proteins ,medicine.anatomical_structure ,Electroporation ,DKK1 ,Gene Expression Regulation ,embryonic structures ,biology.protein ,Cancer research ,WNT3A ,Signal Transduction - Abstract
The dynamic interaction between positive and negative signals is necessary for remodeling of postsynaptic structures at the neuromuscular junction. Here we report that Wnt3a negatively regulates acetylcholine receptor (AChR) clustering by repressing the expression of Rapsyn, an AChR-associated protein essential for AChR clustering. In cultured myotubes, treatment with Wnt3a or overexpression of beta-catenin, the condition mimicking the activation of the Wnt canonical pathway, inhibited Agrin-induced formation of AChR clusters. Moreover, Wnt3a treatment promoted dispersion of AChR clusters, and this effect was prevented by DKK1, an antagonist of the Wnt canonical pathway. Next, we investigated possible mechanisms underlying Wnt3a regulation of AChR clustering in cultured muscle cells. Interestingly, we found that Wnt3a treatment caused a decrease in the protein level of Rapsyn. In addition, Rapsyn promoter activity in cultured muscle cells was inhibited by the treatment with Wnt3a or beta-catenin overexpression. Forced expression of Rapsyn driven by a promoter that is not responsive to Wnt3a prevented the dispersing effect of Wnt3a on AChR clusters, suggesting that Wnt3a indeed acts to disperse AChR clusters by down-regulating the expression of Rapsyn. The role of Wnt/beta-catenin signaling in dispersing AChR clusters was also investigated in vivo by electroporation of Wnt3a or beta-catenin into mouse limb muscles, where ectopic Wnt3a or beta-catenin caused disassembly of postsynaptic apparatus. Together, these results suggest that Wnt/beta-catenin signaling plays a negative role for postsynaptic differentiation at the neuromuscular junction, probably by regulating the expression of synaptic proteins, such as Rapsyn.
- Published
- 2008
45. Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses
- Author
-
Lan Bao, Gang Pei, Ying-Jin Lu, Lu Pu, Chun-Fu Wu, Hua-Ping Fan, Nan-Jie Xu, Guobin Bao, and Xu Zhang
- Subjects
Male ,medicine.medical_specialty ,Amino Acid Transport System X-AG ,Excitatory Amino Acid Transporter 3 ,Presynaptic Terminals ,Glutamic Acid ,Behavioral/Systems/Cognitive ,Neurotransmission ,Hippocampal formation ,Glutamate Plasma Membrane Transport Proteins ,Biology ,Hippocampus ,Rats, Sprague-Dawley ,Glutamatergic ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Cells, Cultured ,Neurons ,Morphine ,Symporters ,General Neuroscience ,Long-term potentiation ,Rats ,Substance Withdrawal Syndrome ,Up-Regulation ,Protein Transport ,Endocrinology ,Excitatory Amino Acid Transporter 2 ,Astrocytes ,Synapses ,Excitatory postsynaptic potential ,Opiate ,Neuroscience ,Morphine Dependence ,Synaptosomes - Abstract
Opiate abuse causes adaptive changes in several processes of synaptic transmission in which the glutamatergic system appears a critical element involved in opiate tolerance and dependence, but the underlying mechanisms remain unclear. In the present study, we found that glutamate uptake in hippocampal synaptosomes was significantly increased (by 70% in chronic morphine-treated rats) during the morphine withdrawal period, likely attributable to an increase in the number of functional glutamate transporters. Immunoblot analysis showed that expression of GLT1 (glutamate transporter subtype 1) was identified to be upregulated in synaptosomes but not in total tissues, suggesting a redistribution of glutamate transporter expression. Moreover, the increase in glutamate uptake was reproduced in cultured neurons during morphine withdrawal, and the increase of uptake in neurons could be blocked by dihydrokainate, a specific inhibitor of GLT1. Cell surface biotinylation and immunoblot analysis showed that morphine withdrawal produced an increase in GLT1 expression rather than EAAC1 (excitatory amino acids carrier 1), a neuronal subtype, at the cultured neuronal cell surface, whereas no significant change was observed in that of cultured astrocytes. Electron microscopy also revealed that GLT1 expression was markedly increased in the nerve terminals of hippocampus and associated with the plasma membranein vivo. These results suggest that GLT1 in hippocampal neurons can be induced to translocate to the nerve terminals and express on the cell surface during morphine withdrawal. The translocation of GLT1 at synapses during morphine withdrawal provides a neuronal mechanism for modulation of excitatory neurotransmission during opiate abuse.
- Published
- 2003
46. Oleamide attenuates apoptotic death in cultured rat cerebellar granule neurons
- Author
-
Jingyu Yang, Kazuho Abe, Nan-Jie Xu, Norio Matsuki, and Chunfu Wu
- Subjects
Cerebellum ,Programmed cell death ,Oleamide ,Cell Survival ,Caspase 3 ,Apoptosis ,Oleic Acids ,chemistry.chemical_compound ,Cerebellar Cortex ,medicine ,Animals ,Propidium iodide ,Rats, Wistar ,Potassium Deficiency ,Caspase ,Cells, Cultured ,Cell Nucleus ,Neurons ,biology ,Dose-Response Relationship, Drug ,General Neuroscience ,Cell Membrane ,Caspase Inhibitors ,Cell biology ,Rats ,medicine.anatomical_structure ,Neuroprotective Agents ,chemistry ,Biochemistry ,Animals, Newborn ,Cerebellar cortex ,Caspases ,biology.protein ,Potassium - Abstract
The effect of oleamide on apoptosis was investigated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay, DNA staining assay with propidium iodide and caspase-3 activity analyses. The present results showed that oleamide significantly attenuated the cell death and nuclear condensation of cultured rat cerebellar granule neurons induced by K(+) deprivation in a dose-dependent manner. The oleamide actions were well parallel with the attenuation of caspase-3 activity in the process of apoptotic death. Moreover, neither elaidic acid nor stearic acid, two fatty acids structurally related to oleamide without the Delta(9)-cis double bond, had similar effects on the cell death, suggesting the selectively structural features of oleamide required for this action. These data provided the first evidence of a protective effect of oleamide against apoptosis in a structurally specific manner.
- Published
- 2002
47. Pseudoginsenoside-F11 attenuates morphine-induced signalling in Chinese hamster ovary-mu cells
- Author
-
Gang Pei, Chun Fu Wu, Wenbo Zhang, Ying Xiong, Hua Ping Fan, Yue Sun, Zhu Li, and Nan Jie Xu
- Subjects
medicine.medical_specialty ,Ginsenosides ,medicine.drug_class ,Narcotic Antagonists ,Pseudoginsenoside F11 ,GTPgammaS ,Receptors, Opioid, mu ,(+)-Naloxone ,CHO Cells ,Biology ,Sulfur Radioisotopes ,Binding, Competitive ,chemistry.chemical_compound ,Opioid receptor ,GTP-Binding Proteins ,Internal medicine ,Cricetinae ,parasitic diseases ,medicine ,Cyclic AMP ,Animals ,Drug Interactions ,Binding Sites ,Dose-Response Relationship, Drug ,Morphine ,General Neuroscience ,Chinese hamster ovary cell ,Cell Membrane ,Saponins ,Analgesics, Opioid ,Endocrinology ,chemistry ,Opioid ,Guanosine 5'-O-(3-Thiotriphosphate) ,Diprenorphine ,Morphine Dependence ,Intracellular ,medicine.drug ,Adenylyl Cyclases ,Signal Transduction - Abstract
Pseudoginsenoside-F11 (PF11), an ocotillol type saponin isolated from Panax quinquefolium L., has been shown to antagonize the behavioral actions of morphine. Biochemical experiments revealed that PF11 could inhibit diprenorphine (DIP) binding with an IC50 of approximately 6.1 microM and reduced the binding potency of morphine in Chinese hamster ovary (CHO)-mu cells. Furthermore, PF11 significantly attenuated morphine-stimulated [35S]GTPgammaS binding in a dose dependent manner, and strongly decreased the efficacy of morphine to inhibit intracellular cAMP production. In addition, PF11 pretreatment could also significantly inhibit naloxone induced cAMP overshoot in the morphine-pretreated cells. However, PF11 per se had no effect on either [35S]GTPgammaS binding or intracellular cAMP accumulation. These data suggested that PF11 antagonized the morphine stimulated opioid receptor signalling directly at the cellular level.
- Published
- 2001
48. Reversal of morphine-induced memory impairment in mice by withdrawal in Morris water maze: possible involvement of cholinergic system
- Author
-
Chunfu Wu, Gang Pei, Nan-Jie Xu, and Zhu Li
- Subjects
Agonist ,Male ,Narcotics ,medicine.medical_specialty ,Physostigmine ,medicine.drug_class ,Injections, Subcutaneous ,Narcotic Antagonists ,Clinical Biochemistry ,Scopolamine ,Morris water navigation task ,(+)-Naloxone ,Muscarinic Antagonists ,Muscarinic Agonists ,Toxicology ,Biochemistry ,Cholinergic Antagonists ,Behavioral Neuroscience ,Mice ,Parasympathetic Nervous System ,Internal medicine ,Oxotremorine ,medicine ,Memory impairment ,Animals ,Maze Learning ,Biological Psychiatry ,Cholinesterase ,Pharmacology ,Memory Disorders ,Motivation ,biology ,Dose-Response Relationship, Drug ,Morphine ,business.industry ,Naloxone ,Substance Withdrawal Syndrome ,Endocrinology ,biology.protein ,business ,medicine.drug - Abstract
The effects of morphine and morphine withdrawal on memory performance were examined in mice by using Morris water maze task. Morphine-induced memory impairment at the doses of 5 and 10 mg/kg recovered after repeated administration. Oxotremorine, a muscarinic receptor agonist, at the dose of 0.1 mg/kg ip, and physostigmine, a cholinesterase inhibitor, at the dose of 0.1 mg/kg ip, significantly antagonized morphine (10 mg/kg sc)-induced memory impairment in mice. Furthermore, repeated naloxone (0.5 mg/kg ip) attenuated scopolamine (0.2 mg/kg ip)-induced memory impairment. By using escalating doses of morphine for 13 days, morphine-induced memory impairment was continuously maintained. When withdrawal was precipitated by naloxone (5 mg/kg ip), or administration of oxotremorine (0.1 and 0.2 mg/kg ip) or physostigmine (0.05 and 0.1 mg/kg ip), the impairment was completely reversed. These results suggest that morphine-induced memory impairment could be partially due to the inhibition of the central cholinergic activity.
- Published
- 2001
49. Reactivation of morphine conditioned place preference by drug priming: role of environmental cues and sensitization
- Author
-
Lin Lu, Nan-Jie Xu, Wen Yue, Xin Ge, Wenjuan Su, Gang Pei, and Lan Ma
- Subjects
Male ,Narcotics ,medicine.drug_class ,Craving ,(+)-Naloxone ,Pharmacology ,Environment ,Heroin ,Rats, Sprague-Dawley ,Opioid receptor ,Conditioning, Psychological ,medicine ,Animals ,Sensitization ,Dose-Response Relationship, Drug ,Morphine ,Extinction (psychology) ,Opioid-Related Disorders ,Conditioned place preference ,Rats ,medicine.anatomical_structure ,medicine.symptom ,Cues ,Psychology ,medicine.drug - Abstract
Rationale: Relapse is a major characteristic of drug addiction and remains the primary problem in treating drug abuse. Despite a great deal of research, the exact factors that determine renewed drug-seeking and persistent craving for them remain unclear. Objective: The present study was designed to evaluate the role of environmental cues and behavioral sensitization in reactivation of place preference following long-term extinction of morphine conditioned place preference (CPP) in rats. Methods: After being injected with morphine and saline alternately for 6 days to induce morphine CPP, the rats were subjected to extinction of conditioning for 21 days. The rats were then administered various doses of morphine, heroin, or cocaine and confined in the previous drug- or saline-paired compartment. CPP was determined. Some rats were treated with scopolamine or naloxone prior to administration of these three drugs. Results: Morphine CPP disappeared following a 21-day extinction. A single injection of morphine, heroin, or cocaine evoked place preference for the previous drug-paired side. However, place preference for the previous vehicle-paired side was induced after the animals received a single injection of morphine, heroin or cocaine and confined to the previous vehicle-paired compartment. Administration of naloxone prior to drug treatment significantly attenuated the place preference induced by morphine or heroin, but had no significant effect on the place preference elicited by cocaine. Administration of the cholinergic antagonist scopolamine before morphine, heroin and cocaine inhibited the expression of place preference. Conclusions: Environment-related cues and behavioral sensitization play critical roles in the incentive motivation underlying drug-seeking behaviors.
- Published
- 2000
50. Rapsyn Interaction with Calpain Stabilizes AChR Clusters at the Neuromuscular Junction
- Author
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Lin Mei, Ying Huang, Yu-Qiang Ding, Jia Wang, Lei Qian, Zhi Hua Yang, Zhen-Ge Luo, Nan Jie Ruan, Fei Chen, Shyuan T. Ngo, Claudio Schneider, and Peter G. Noakes
- Subjects
animal structures ,Neuroscience(all) ,Muscle Fibers, Skeletal ,Synaptogenesis ,Neuromuscular Junction ,Synaptic Membranes ,Muscle Proteins ,Mice, Transgenic ,Biology ,Cholinergic Agonists ,Neuromuscular junction ,MOLNEURO ,Cell Line ,Mice ,medicine ,Animals ,Humans ,Receptors, Cholinergic ,Agrin ,Acetylcholine receptor ,Calpastatin ,Calpain ,General Neuroscience ,Calcium-Binding Proteins ,Receptor Aggregation ,musculoskeletal system ,Molecular biology ,Cell biology ,medicine.anatomical_structure ,SIGNALING ,biology.protein ,Cholinergic ,Carbachol ,CELLBIO ,Acetylcholine ,medicine.drug ,Signal Transduction - Abstract
SummaryAgrin induces, whereas acetylcholine (ACh) disperses, ACh receptor (AChR) clusters during neuromuscular synaptogenesis. Such counteractive interaction leads to eventual dispersal of nonsynaptic AChR-rich sites and formation of receptor clusters at the postjunctional membrane. However, the underlying mechanisms are not well understood. Here we show that calpain, a calcium-dependent protease, is activated by the cholinergic stimulation and is required for induced dispersion of AChR clusters. Interestingly, the AChR-associated protein rapsyn interacted with calpain in an agrin-dependent manner, and this interaction inhibited the protease activity of calpain. Disrupting the endogenous rapsyn/calpain interaction enhanced CCh-induced dispersion of AChR clusters. Moreover, the loss of AChR clusters in agrin mutant mice was partially rescued by the inhibition of calpain via overexpressing calpastatin, an endogenous calpain inhibitor, or injecting calpeptin, a cell-permeable calpain inhibitor. These results demonstrate that calpain participates in ACh-induced dispersion of AChR clusters, and rapsyn stabilizes AChR clusters by suppressing calpain activity.
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