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1.
Neurobiol Aging ; 89: 142.e1-142.e7, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32081467

RESUMO

Recently, the (GGC)n repeat expansion in the NOTCH2NLC gene has been identified to be associated with neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of dementia-dominant NIID with neurodegenerative dementia, we therefore hypothesized that the NOTCH2NLC repeat expansion might also contribute to these diseases. In the present study, repeat primed polymerase chain reaction (RP-PCR) and GC-rich PCR were conducted to detect the repeats of NOTCH2NLC in a cohort of 1004 patients with neurodegenerative dementias from mainland China. As a result, 4 sporadic patients were found to carry the NOTCH2NLC repeats expansion, totally accounting for 0.4% of all dementia individuals, and the accurate repeated sizes were 110, 133,120 and 76 respectively. Of 4 mutation carriers, three and one were clinically diagnosed Alzheimer's disease (AD) and frontotemporal dementia (FTD) respectively. In addition, 3 out of them revealed leukoencephalopathy in T2-Flair imaging. This study revealed that although rare, the NOTCH2NLC repeat expansions may be associated with AD or FTD-like phenotype as well as leukoencephalopathy.

2.
Burns ; 46(2): 423-429, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866180

RESUMO

PURPOSE: The Formosa Fun Coast Explosion was a major public disaster that caused international shock. Nursing staff made an all-out effort to care for patients injured in the explosion, and this may have caused a lot of stress among nurses. This study aimed to explore the predictors of professional quality of life among nursing staff experiencing major disaster events. MATERIAL AND METHODS: This descriptive cross-sectional study was conducted in a medical center in Northern Taiwan in 2016. A total of 165 nurses were enrolled using convenience sampling. Data were collected on the demographic- and work-related characteristics of nurses, and the Perceived Stress Scale and Professional Quality of Life Scale were administered. Analyses included descriptive statistics and regression. The threshold for statistical significance was set at p<0.05. RESULTS: The nurses' length of service in nursing (ß=-0.26, p=0.029) and perceived stress level (ß=0.15, p=0.002) were important predictors of compassion satisfaction, while their age (ß=0.42, p=0.033) and perceived stress level (ß=0.20, p=0.020) were important predictors of compassion fatigue. Compassion fatigue was divided into burnout and secondary trauma. Nurses' age (ß=0.18, p=0.044) and perceived stress level (ß=0.14, p<0.001) were the key predictors of burnout. However, there were no significant predictors of secondary trauma among nurses. CONCLUSIONS: Based on the present findings, it is proposed to reduce the level of stress among nurses to improve their professional quality of life.

3.
J Immunother Cancer ; 7(1): 326, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775862

RESUMO

BACKGROUND: It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy. METHODS: A novel EVs-liked ginseng-derived nanoparticles (GDNPs) were isolated and characterized from Panax ginseng C. A. Mey. Using GDNPs as an immunopotentiator for altering M2 polarized macrophages, we analyzed associated surface markers, genes and cytokines of macrophages treated with GDNPs. Mice bearing B16F10 melanoma were treated with GDNPs therapy. Tumor growth were assessed, and TAM populations were evaluated by FACS and IF. RESULTS: GDNPs significantly promoted the polarization of M2 to M1 phenotype and produce total reactive oxygen species, resulting in increasing apoptosis of mouse melanoma cells. GDNP-induced M1 polarization was found to depend upon Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88)-mediated signaling. Moreover, ceramide lipids and proteins of GDNPs may play an important role in macrophage polarization via TLR4 activation. We found that GDNPs treatment significantly suppressed melanoma growth in tumor-bearing mice with increased presence of M1 macrophages detected in the tumor tissue. CONCLUSIONS: GDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy.

4.
Ying Yong Sheng Tai Xue Bao ; 29(8): 2551-2558, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30182594

RESUMO

Winter wheat and summer maize were the main crops in the North China Plain. While intensive farming system could generally achieve high yield, the perennial large amounts of nitrogen (N) fertilization application cause environmental problems including NO3--N accumulation and leaching at deep soil layer. Here, the effects of different N application rates on soil NO3--N accumulation and leaching in winter wheat-summer maize cropping system were investigated from 2010 to 2016 at Qingyuan County, Hebei Province, China. There were five treatments with N application rates at 0 (N0), 100 (N100), 180 (N180), 255 (N255) and 330 (N330) kg·hm-2. Results showed that crop yield and soil N status significantly varied among treatments for both wheat and maize after each harvest, respectively. Soil NO3--N were accumulated during winter wheat growing season and leached to deeper soil during summer maize growing season. Moreover, the soil NO3--N accumulation amount in the 90 to 180 cm soil profile decreased with the decreases of N inputs (N330 > N255 > N180 > N100 > N0). Soil NO3--N could be leached to 990 cm soil depth. There were six NO3--N accumulation peaks in the soil profile, with the peaks presenting at deeper soil profile with higher N fertilization rate. The deepest peak appeared at 840 cm soil depth with the N application rate of 330 kg·hm-2. From the distribution of NO3--N accumulation in the soil profile, only around 10% of total NO3--N was accumulated between 0-90 cm soil depth, while the rest accumulated below 90 cm, which could not be largely absorbed by plants. Therefore, NO3--N leaching during summer maize growing season was serious and it was greater with higher N fertilization rate which might lead to increased risk of underground water contamination. In terms of balanced crop yield and soil NO3--N accumulation, the rate of 180 kg·hm-2 would be the optimum one in areas with similar cultivation and environmental conditions to the present study.


Assuntos
Produtos Agrícolas , Nitrogênio , Triticum , Zea mays , Agricultura , China , Fertilizantes , Nitratos , Rotação , Estações do Ano , Solo
5.
Clin Nurs Res ; : 1054773818793599, 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-30094998

RESUMO

Although the survival rate of burn patients in the Formosa Fun Coast Explosion disaster increased significantly, for patients facing long-term rehabilitation, there remained great stress. Therefore, the aim of this study was to explore the predictors of resilience among burn patients in this major disaster. We conducted a cross-sectional, descriptive study in a medical center in northern Taiwan, with a total of 30 burn patients enrolled. Patients' demographics were collected, and the Resilience Scale and Perceived Stress Scale were administered. Multivariate statistical analysis by stepwise and linear regression was used to test these predictors of resilience. The results showed that perceived stress was the key predictor of resilience in the stepwise regression analysis and by adjusting variables including stress level, gender, and education level. These results indicate that the stress level of burn patients should be determined first to provide more targeted methods for reducing stress and improving resilience.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(3): 309-313, 2018 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-29896721

RESUMO

OBJECTIVE: To determine the frequency of spinocerebellar ataxia type 31 (SCA31) related mutations among patients from mainland China. METHODS: For a cohort of molecularly unassigned patients comprised of 295 SCA patients (including 98 probands from families featuring autosomal dominant SCA and 197 sporadic cases) and 81 patients with hereditary spastic paraplegia (HSP) (including 23 probands from families with autosomal dominant HSP and 58 sporadic cases),TGGAA pentanucleotide expansion insertional mutation of the BEAN/TK2 gene was detected using repeat-primed PCR followed by capillary gel electrophoresis. RESULTS: No TGGAA pentanucleotide insertion expansion in BEAN/TK2 gene was identified in the above cohort. CONCLUSION: SCA31 is an extremely rare subtype of SCA and should not be included in routine genetic screening in mainland China.


Assuntos
Ataxias Espinocerebelares/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Criança , China , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Paraplegia Espástica Hereditária/genética , Adulto Jovem
7.
Mol Neurodegener ; 13(1): 4, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29378605

RESUMO

BACKGROUND: Spinocerebellar ataxia 17 (SCA17) belongs to the family of neurodegenerative diseases caused by polyglutamine (polyQ) expansion. In SCA17, polyQ expansion occurs in the TATA box binding protein (TBP) and leads to the misfolding of TBP and the preferential degeneration in the cerebellar Purkinje neurons. Currently there is no effective treatment for SCA17. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a recently identified neurotrophic factor, and increasing MANF expression ameliorated SCA17 neuropathology in TBP-105Q knock-in (KI) mouse model, indicating that MANF could be a therapeutic target for treating SCA17. METHODS: In this study, we screened a collection of 2000 FDA-approved chemicals using a stable cell line expressing luciferase reporter, which is driven by MANF promoter. We identified several potential candidates that can induce the expression of MANF. Of these inducers, piperine is an agent that potently induces the luciferase expression or MANF expression. RESULTS: Addition of piperine in both cellular and mouse models of SCA17 alleviated toxicity caused by mutant TBP. Although mutant TBP is primarily localized in the nuclei, the polyQ expansion in TBP is able to induce ER stress, suggesting that nuclear misfolded proteins can also elicit ER stress as cytoplasmic misfolded proteins do. Moreover, piperine plays its protective role by reducing toxicity caused by the ER stress. CONCLUSION: Our study established piperine as a MANF-based therapeutic agent for ER stress-related neuropathology in SCA17.


Assuntos
Alcaloides/farmacologia , Benzodioxóis/farmacologia , Encéfalo/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fatores de Crescimento Neural/biossíntese , Fármacos Neuroprotetores/farmacologia , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Degeneração Neural/patologia , Fatores de Crescimento Neural/efeitos dos fármacos , Proteína de Ligação a TATA-Box/toxicidade
8.
Sci Transl Med ; 9(416)2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29141887

RESUMO

The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit is completely unpredictable, thus raising concerns about MSC efficacy. One of the affecting factors is the unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding the fate of infused MSCs could help predict clinical responses. Using a murine model of graft-versus-host disease (GvHD), we demonstrate that MSCs are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression. When examining patients with GvHD who received MSCs, we found a striking parallel, whereby only those with high cytotoxic activity against MSCs responded to MSC infusion, whereas those with low activity did not. The need for recipient cytotoxic cell activity could be replaced by the infusion of apoptotic MSCs generated ex vivo. After infusion, recipient phagocytes engulf apoptotic MSCs and produce indoleamine 2,3-dioxygenase, which is ultimately necessary for effecting immunosuppression. Therefore, we propose the innovative concept that patients should be stratified for MSC treatment according to their ability to kill MSCs or that all patients could be treated with ex vivo apoptotic MSCs.


Assuntos
Apoptose/fisiologia , Células-Tronco Mesenquimais/citologia , Animais , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Imunomodulação/genética , Imunomodulação/fisiologia , Imunossupressão/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia
9.
Can J Infect Dis Med Microbiol ; 2017: 7058396, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29147117

RESUMO

This study included fifty-eight isolates of P. aeruginosa from the oral cavity of snakes that were recruited from clinical cases, captive and wild snakes. The minimum inhibitory concentrations (MICs) for the determination of susceptibility were identified by the broth microdilution method. Polymerase chain reaction (PCR) was employed to detect ß-lactamases genes. With regard to antipseudomonal antibiotics, the lowest nonsusceptible rates were in aztreonam (15%), piperacillin/tazobactam (12%), and amikacin (9%). The nonsusceptible rates were high in gentamicin (33%) and colistin (55%). Meanwhile, blaTEM presented in 100% of isolates where blaAmpC, blaOXA-1, and blaOXA-10 came at 94.8%, 89.7%, and 27.6%, respectively. Emergence of multidrug resistant (MDR) strains and colistin-resistant strains highlights the potential breach of public health as P. aeruginosa could be transmitted through either direct contact or indirect dissemination through the environment. This study reports that the highly resistant P. aeruginosa from snakes' oral cavity were discovered for the very first time in Taiwan.

10.
Mamm Genome ; 28(5-6): 220-226, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28500484

RESUMO

In this study, we aimed to investigate the association of four single nucleotide polymorphisms (SNPs) (MTHFR 677 C > T, MTHFR 1298 A > C, MTR 2756 A > G and MTRR 66 A > G), gene-gene interaction and haplotype combination with pulmonary embolism (PE) risk based on Chinese Han population. Logistic regression was performed to investigate association between four SNPs within folate metabolism gene and PE risk, and GMDR model was used to investigate the additional gene-gene interactions among the four SNPs. Logistic analysis showed that rs1801133 and rs1801131 in MTHFR gene were associated with increased PE risk in both additive and dominant models. The carriers with homozygous mutant of rs1801133 polymorphism and homozygous of rs1801131 were associated with increased PE risk, and ORs (95% CI) were 1.71(1.24-2.21) and 1.58 (1.24-2.01), respectively. We also found a significant gene-gene interaction between rs1801133 and rs1801131 on PE. Overall, the cross-validation consistency of this two-locus model was 10/10, and the testing accuracy was 60.72%, after adjusting for covariates. Haplotype containing the rs1801133- T and rs1801131- C alleles were associated with a statistically increased PE risk, OR (95% CI) = 2.68 (1.28-4.13), P < 0.001. We found that rs1801133 and rs1801131 within MTHFR gene, their interaction, and haplotype containing the rs1801133- T and rs1801131- C alleles were all associated with PE risk.


Assuntos
Ácido Fólico/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Embolia Pulmonar/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Ferredoxina-NADP Redutase/genética , Ácido Fólico/metabolismo , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Embolia Pulmonar/metabolismo , Embolia Pulmonar/patologia , Fatores de Risco
11.
Cortex ; 90: 71-87, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28365490

RESUMO

Consciousness loss in patients with severe brain injuries is associated with reduced functional connectivity of the default mode network (DMN), fronto-parietal network, and thalamo-cortical network. However, it is still unclear if the brain white matter connectivity between the above mentioned networks is changed in patients with disorders of consciousness (DOC). In this study, we collected diffusion tensor imaging (DTI) data from 13 patients and 17 healthy controls, constructed whole-brain white matter (WM) structural networks with probabilistic tractography. Afterward, we estimated and compared topological properties, and revealed an altered structural organization in the patients. We found a disturbance in the normal balance between segregation and integration in brain structural networks and detected significantly decreased nodal centralities primarily in the basal ganglia and thalamus in the patients. A network-based statistical analysis detected a subnetwork with uniformly significantly decreased structural connections between the basal ganglia, thalamus, and frontal cortex in the patients. Further analysis indicated that along the WM fiber tracts linking the basal ganglia, thalamus, and frontal cortex, the fractional anisotropy was decreased and the radial diffusivity was increased in the patients compared to the controls. Finally, using the receiver operating characteristic method, we found that the structural connections within the NBS-derived component that showed differences between the groups demonstrated high sensitivity and specificity (>90%). Our results suggested that major consciousness deficits in DOC patients may be related to the altered WM connections between the basal ganglia, thalamus, and frontal cortex.


Assuntos
Gânglios da Base/fisiopatologia , Transtornos da Consciência/fisiopatologia , Estado de Consciência/fisiologia , Lobo Frontal/fisiopatologia , Tálamo/fisiopatologia , Adolescente , Adulto , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Substância Branca/fisiopatologia , Adulto Jovem
12.
Neurobiol Aging ; 53: 192.e5-192.e10, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28094059

RESUMO

DNA methylation has been acknowledged as one of the key epigenetic mechanisms involved in the regulation of gene expression and genomic functions. Alteration of the DNA methylation level has been linked to modification of the disease progression and instability regulation of certain disease-causing repeats in neurodegenerative diseases. In this study, blood samples collected from spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) patients versus control were used to explore the potential link of DNA methylation levels at ATXN3 gene promoter to the pathogenesis of SCA3/MJD. We found that the methylation levels in the ATXN3 promoter were significantly higher in SCA3/MJD patients relative to the controls. Furthermore, higher methylation levels were detected in the SCA3/MJD patients with earlier age at onset and the families with an intergenerational CAG repeats instability. In addition, the first CpG island of the ATXN3 promoter served as the main regulation region of DNA methylation. These findings suggested that an epigenetic change may contribute to the pathogenesis of the SCA3/MJD and provide potential therapeutic targets for CAG repeats-based diseases.


Assuntos
Ataxina-3/genética , Metilação de DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Doença de Machado-Joseph/genética , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/genética , Adulto , Células Cultivadas , Ilhas de CpG/genética , Ilhas de CpG/fisiologia , Progressão da Doença , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Repetições de Trinucleotídeos/genética
13.
Brain Imaging Behav ; 11(2): 430-443, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26860909

RESUMO

Although previous studies reported altered topology of brain functional networks in patients with Parkinson's disease (PD), the modular organization of brain functional networks in PD patients remains largely unknown. Using the resting-state functional MRI (R-fMRI) and graph theory, we examined the modular organization of brain functional networks in 32 unmedicated patients with early-to-mid motor stage PD and 31 healthy controls. Compared to the controls, the PD patients tended to show decreased integrity and segregation, both within and between modules. This was inferred by significantly increased intra-modular characteristic path length (L p) within four modules: mPFC, SN, SMN, and FPN, decreased inter-modular functional connectivity (FC) between mPFC and SN, SMN, and VN, and decreased intra-modular clustering in the PD patients. Intra-modular characteristic path length within the mPFC showed significantly positive correlation with general cognitive ability in the PD group. Receiver operating characteristic (ROC) analysis revealed that FC between mPFC and SN had the highest significant accuracy in differentiating the patients from the controls. Our findings may provide new insight in understanding the pathological changes that underlie impairment in cognition and movement in Parkinson's disease.


Assuntos
Adaptação Fisiológica , Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Doença de Parkinson/fisiopatologia , Simulação por Computador , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
14.
Sci Rep ; 6: 38866, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27958328

RESUMO

Existing evidence suggests that the default-mode network (DMN) and fronto-pariatal network (FPN) play an important role in altered states of consciousness. However, the brain mechanisms underlying impaired consciousness and the specific network interactions involved are not well understood. We studied the topological properties of brain functional networks using resting-state functional MRI data acquired from 18 patients (11 vegetative state/unresponsive wakefulness syndrome, VS/UWS, and 7 minimally conscious state, MCS) and compared these properties with those of healthy controls. We identified that the topological properties in DMN and FPN are anti-correlated which comes, in part, from the contribution of interactions between dorsolateral prefrontal cortex of the FPN and precuneus of the DMN. Notably, altered nodal connectivity strength was distance-dependent, with most disruptions appearing in long-distance connections within the FPN but in short-distance connections within the DMN. A multivariate pattern-classification analysis revealed that combination of topological patterns between the FPN and DMN could predict conscious state more effectively than connectivity within either network. Taken together, our results imply distinct interactions between the FPN and DMN, which may mediate conscious state.


Assuntos
Lobo Frontal/fisiopatologia , Lobo Parietal/fisiopatologia , Estado Vegetativo Persistente/fisiopatologia , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Vias Neurais/fisiopatologia
15.
Oncotarget ; 7(49): 81698-81714, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27835581

RESUMO

In this article we inspect the roles and functions of the methyl-CpG-binding domain protein 3 (MBD3) in human malignant glioma, to assess its potential as an epigenetic biomarker for prognosis. The regulatory effects of MBD3 on glioma transcriptome were first profiled by high-throughput microarray. Our results indicate that MBD3 is involved in both transcriptional activation and repression. Furthermore, MBD3 fine-controls a spectrum of proteins critical for cellular metabolism and proliferation, thereby contributing to an exquisite anti-glioma network. Specifically, the expression of MHC class II molecules was found to positively correlate with MBD3, which provides new insight into the immune escape of gliomagenesis. In addition, MBD3 participates in constraining a number of oncogenic non-coding RNAs whose over-activation could drive cells into excessive growth and higher malignancy. Having followed up a pilot cohort, we noted that the survival of malignant glioma patients was proportional to the content of MBD3 and 5-hydroxymethylcytosine (5hmC) in their tumor cells. The progression-free survival (PFS) and overall survival (OS) were relatively poor for patients with lower amount of MBD3 and 5hmC in the tissue biopsies. Taken together, this work enriches our understanding of the mechanistic involvement of MBD3 in malignant glioma.


Assuntos
Neoplasias Encefálicas/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Perfilação da Expressão Gênica/métodos , Glioma/metabolismo , Glioma/mortalidade , Glioma/patologia , Antígenos HLA-D/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Projetos Piloto , Interferência de RNA , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Transdução de Sinais , Fatores de Tempo , Transcrição Genética , Transfecção
16.
J Nanosci Nanotechnol ; 16(2): 1638-44, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27433637

RESUMO

Silver nanorods/polyimide (Ag-NRs/PI) nanocomposites with high conductivity (An order of magnitude higher than pure PI), frequency-independent dielectric permittivity (3.8-4.2) and low dielectric loss (<0.05) were prepared by an in-situ polymerization process. Ag-nanorods with a mean width of approximately 300 nm and an average length over 8 microm were synthesized in the presence of polyvinylpyrrolidone (PVP) and NaCl by polyol process. SEM images showed that metallic Ag-nanorods were well dispersed in PI matrix. The structure of Ag-NRs was not destroyed or changed in nanocomposite films and the order of PI molecular chains was maintained as well. The orientation of the Ag-NRs in the PI matrix improved the mechanical properties of nanocomposite films. TGA results showed that the thermal property of nanocomposite films was almost as good as pure PI.

17.
Neurobiol Aging ; 46: 235.e11-5, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27311648

RESUMO

Frontotemporal dementia (FTD) is a clinically heterogeneous neurodegenerative disorder, including behavior behavioral variant FTD (bvFTD), semantic dementia, progressive nonfluent aphasia (PNFA), FTD-parkinsonism, and FTD-motor neuron disease. To date, there are at least 8 causative genes identified in patients with FTD. Among them, variants in the microtubule-associated protein tau (MAPT), GRN, and chromosome 9 open-reading frame 72 (C9orf72) genes are considered the major cause of FTD. To date, no comprehensive analyses of mutations in these 3 genes have been conducted in the Chinese population. In this study, we screened all exons of MAPT, and GRN, as well as GGGGCC repeats in C9orf72 in a cohort of 52 patients from mainland China, including 38 bvFTD, 7 PNFA, 2 semantic dementia, and 5 FTD-parkinsonism. As a result, 2 novel mutations in MAPT (p.D177V and p.P513A) were identified in a sporadic and familial patient with PNFA respectively, and one known mutation in MAPT (p.N279K) was detected in an FTD-parkinsonism family. In addition, one reported nonsense mutation (p.Q300Term) in GRN was found in a sporadic patient with bvFTD. Finally, no pathogenic GGGGCC repeats in C9orf72 were detected in any case. To our knowledge, this is the first cohort report screening for common causative mutations in patients with FTD in the Chinese population. Our findings indicate that variants of MAPT and GRN are a common cause of FTD in mainland China.


Assuntos
Demência Frontotemporal/genética , Estudos de Associação Genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação/genética , Proteínas/genética , Proteínas tau/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Proteína C9orf72 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Progranulinas
18.
Int J Oncol ; 48(2): 541-50, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26648487

RESUMO

MicroRNAs (miRs) have been found to play important roles in mediating a variety of biological processes in human cancers, including tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). In the present study, we aimed to investigate the putative role of miR­200b in the progression of glioma. Real-time RT-PCR data showed that the miR­200b levels were frequently reduced in primary glioma tissues (n=88) and cell lines, when compared to normal brain tissues (n=25). Moreover, decreased miR­200b level was tightly associated with the malignant progression of glioma. Overexpression of miR­200b significantly suppressed cell proliferation, migration, invasion and EMT in glioma U251 and U87 cells. Luciferase reporter assay data further identified ZEB2 as a direct target of miR­200b, and the protein expression of ZEB2 was markedly reduced after overexpression of miR­200b in U251 and U87 cells. Furthermore, restoration of ZEB2 effectively reversed the reduced expression of ZEB2, as well as the suppressive effects of miR­200b overexpression on the proliferation, migration, invasion and EMT in glioma U251 and U87 cells. Moreover, in vivo study showed that overexpression of miR­200b significantly inhibited tumorigenesis as well as the tumor growth of glioma cells, and effectively protected nude mice from tumor-induced death. Taken together these findings suggest that miR­200b has suppressive effects on the proliferation, migration, invasion and EMT of glioma cells, partly at least, via targeting ZEB2. Therefore, miR­200b acts as a novel tumor suppressor in glioma, and thus may become a promising therapeutic candidate for glioma.


Assuntos
Proliferação de Células/genética , Glioma/genética , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Metástase Neoplásica/genética , Proteínas Repressoras/genética , Adulto , Idoso , Animais , Apoptose/genética , Neoplasias Encefálicas/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Adulto Jovem , Homeobox 2 de Ligação a E-box com Dedos de Zinco
19.
J Agric Food Chem ; 63(51): 10948-56, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26653826

RESUMO

Matrix metalloproteinases (MMPs) are proposed to play important roles in the degradation of collagens, thus causing the post-mortem softening of fish muscle, although the specific mechanism remains largely unresolved. Previously, we reported the existence of gelatinase-like proteinases in common carp (Cyprinus carpio) muscle. The primary structures of these proteinases, however, have never been investigated. In the present study, two MMPs with molecular masses of 66 and 65 kDa were purified to homogeneity from common carp muscle by ammonium sulfate fractionation and a series of column chromatographies. Matrix-assisted laser desorption/ionization-tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS/MS) analysis indicated that they are completely identical to MMP-2 from common carp. During chilled storage of common carp at 4 °C, the enzymatic activity of MMP-2 increased to 212% in 12 h while the texture profile increased over the first 2 h and gradually decreased. On the other hand, type V collagen was purified to homogeneity and a specific polyclonal antibody against this protein was prepared. Both type I and V collagens were effectively hydrolyzed by MMP-2 at 30 °C and even at 4 °C. Furthermore, injection of metalloproteinase proteinase inhibitor EDTA into the blood vessel of live common carp suppressed post-mortem tenderization significantly. All of these results confirmed that MMP-2 is a major proteinase responsible for the degradation of collagens, resulting in the softening of fish muscle during chilled storage.


Assuntos
Carpas , Colágeno/metabolismo , Conservação de Alimentos/métodos , Metaloproteinase 2 da Matriz/metabolismo , Músculos/metabolismo , Alimentos Marinhos/análise , Animais , Temperatura Baixa , Colágeno Tipo I/metabolismo , Colágeno Tipo V/metabolismo , Músculos/enzimologia , Sensação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
20.
PLoS One ; 10(8): e0136245, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26295349

RESUMO

BACKGROUND: A number of hereditary neurological diseases display indistinguishable features at the early disease stage. Parkinsonian symptoms can be found in numerous diseases, making it difficult to get a definitive early diagnosis of primary causes for patients with onset of parkinsonism. The accurate and early diagnosis of the causes of parkinsonian patients is important for effective treatments of these patients. METHODS: We have identified a Chinese family (82 family members over four generations with 21 affected individuals) that manifested the characterized symptoms of parkinsonism and was initially diagnosed as Parkinson's disease. We followed up with the family for two years, during which we carried out clinical observations, Positron Emission Tomography-Computed Tomography neuroimaging analysis, and exome sequencing to correctly diagnose the case. RESULTS: During the two-year follow-up period, we performed comprehensive medical history collection, physical examination, and structural and functional neuroimaging studies of this Chinese family. We found that the patient exhibited progressive deteriorated parkinsonism with Parkinson disease-like neuropathology and also had a good response to the initial levodopa treatment. However, exome sequencing identified a missense mutation, N279K, in exon 10 of MAPT gene, verifying that the early parkinsonian symptoms in this family are caused by the genetic mutation for hereditary frontotemporal lobar dementia. CONCLUSIONS: For the inherited parkinsonian patients who even show the neuropathology similar to that in Parkinson's disease and have initial response to levodopa treatment, genetic identification of the molecular basis for the disease is still required for defining the early diagnosis and correct treatment.


Assuntos
Transtornos Parkinsonianos/genética , Adulto , Idade de Início , Grupo com Ancestrais do Continente Asiático/genética , Encéfalo/patologia , Exoma/genética , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto/genética , Neuroimagem , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/patologia , Linhagem , Tomografia por Emissão de Pósitrons , Proteínas tau/genética
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