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1.
Int J Cardiol ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412175
2.
Nat Commun ; 11(1): 6322, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303760

RESUMO

Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4+ macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3+ T cells with high proportion of TIGIT+ cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.

3.
J Transl Med ; 18(1): 436, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198777

RESUMO

BACKGROUND: Squamous cell carcinoma (SCC) is a main pathological type of non-small cell lung cancer. It is common among elderly patients with poor prognosis. We aimed to establish an accurate nomogram to predict survival for elderly patients (≥ 60 years old) with SCC based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The gerontal patients diagnosed with SCC from 2010 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The independent prognostic factors were identified using multivariate Cox proportional hazards regression analysis, which were utilized to conduct a nomogram for predicting survival. The novel nomogram was evaluated by Concordance index (C-index), calibration curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). RESULTS: 32,474 elderly SCC patients were included in the analysis, who were randomly assigned to training cohort (n = 22,732) and validation cohort (n = 9742). The following factors were contained in the final prognostic model: age, sex, race, marital status, tumor site, AJCC stage, surgery, radiation and chemotherapy. Compared to AJCC stage, the novel nomogram exhibited better performance: C-index (training group: 0.789 vs. 0.730, validation group: 0.791 vs. 0.733), the areas under the receiver operating characteristic curve of the training set (1-year AUC: 0.846 vs. 0.791, 3-year AUC: 0.860 vs. 0.801, 5-year AUC: 0.859 vs. 0.794) and the validation set (1-year AUC: 0.846 vs. 0.793, 3-year AUC: 0.863 vs. 0.806, 5-year AUC: 0.866 vs. 0.801), and the 1-, 3- and 5-year calibration plots. Additionally, the NRI and IDI and 1-, 3- and 5-year DCA curves all confirmed that the nomogram was a great prognosis tool. CONCLUSIONS: We constructed a novel nomogram that could be practical and helpful for precise evaluation of elderly SCC patient prognosis, thus helping clinicians in determining the appropriate therapy strategies for individual SCC patients.

4.
Biosens Bioelectron ; 170: 112662, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032198

RESUMO

Cancer cell enumeration and phenotyping can predict the prognosis and the therapy efficacy in patients, yet it remains challenging to detect the rare tumor cells. Herein, we report an octopus-inspired, bifunctional aptamer signal amplifier-based cytosensor (OApt-cytosensor) for sensitive cell analysis. By assembling high-affinity antibodies on an electrode surface, the target cells could be specifically captured and thus been sandwiched by the cell surface marker-specific DNA aptamers. These on-cell aptamers function as electrochemical signal amplifiers by base-selective electronic doping with methylene blue. Such a sandwich configuration enables highly sensitive cell detection down to 10 cells/mL (equal to ~1-2 cells at a sampling volume of 150 µL), even in a large excess of nontarget blood cells. This approach also reveals the cell-surface markers and tracks the cellular epithelial-to-mesenchymal transition induced by signaling regulators. Furthermore, the electron-doped aptamer shows remarkable cell fluorescent labeling that guides the release of the captured cells from electrode surface via electrochemistry. These features make OApt-cytosensor a promising tool in revealing the heterogeneous cancer cells and anticancer drug screening at the single-cell level.

5.
J Cancer Res Ther ; 16(5): 960-966, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004735

RESUMO

As a treatment option for cancer, thermal ablation has satisfactory effects on many types of solid tumors (such as liver and renal cancers). However, its clinical applications for the treatment of thyroid nodules and metastatic cervical lymph nodes are still under debate both in China and abroad. In 2015, the "Zhejiang Expert consensus on thermal ablation for thyroid benign nodules, microcarcinoma, and metastatic cervical lymph nodes (2015 edition)," was released by the Thyroid Cancer Committee of Zhejiang Anti-Cancer Association, China. To further standardize the application of thermal ablation for thyroid tumors, the Thyroid Tumor Ablation Experts Group of Chinese Medical Doctor Association has organized many seminars and finally produced a consensus to formulate the "Expert consensus workshop report: Guidelines for thermal ablation of thyroid tumors (2019 edition)."

6.
Evol Bioinform Online ; 16: 1176934320954868, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32952395

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive and fatal sub-type of breast cancer. This study aimed to identify metastasis-associated genes that could serve as biomarkers for TNBC diagnosis and prognosis. RNA-seq data and clinical information on TNBC from the Cancer Genome Atlas were used to conduct analyses. Expression data were used to establish co-expression modules using average linkage hierarchical clustering. We used weighted gene co-expression network analysis to explore the associations between gene sets and clinical features and to identify metastasis-associated candidate biomarkers. The K-M plotter website was used to explore the association between the expression of candidate biomarkers and patient survival. In addition, receiver operating characteristic curve analysis was used to illustrate the diagnostic performance of candidate genes. The pale turquoise module was significantly associated with the occurrence of metastasis. In this module, 64 genes were identified, and its functional enrichment analysis revealed that they were mainly associated with transcriptional misregulation in cancer, microRNAs in cancer, and negative regulation of angiogenesis. Further, 4 genes, IGSF10, RUNX1T1, XIST, and TSHZ2, which were negatively associated with relapse-free survival and have seldom been reported before in TNBC, were selected. In addition, the mRNA expression levels of the 4 candidate genes were significantly lower in TNBC tumor tissues compared with healthy tissues. Based on the K-M plotter, these 4 genes were correlated with poor prognosis of TNBC. The area under the curve of IGSF10, RUNX1T1, TSHZ2, and XIST was 0.918, 0.957, 0.977, and 0.749. These findings provide new insight into TNBC metastasis. IGSF10, RUNX1T1, TSHZ2, and XIST could be used as candidate biomarkers for the diagnosis and prognosis of TNBC metastasis.

7.
Arch Gynecol Obstet ; 302(3): 685-692, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32602000

RESUMO

BACKGROUND: Recent studies show that contrast-enhanced ultrasonography (CEUS) using SonoVue has the potential to improve the performance of sentinel lymph node biopsy (SLNB) in patients with early breast cancer. However, the evidence of SLNB using CEUS in patients converting from cN1 to cN0 after neoadjuvant chemotherapy (NAC) is lacking. The aim of this prospective study is to evaluate the feasibility of CEUS using SonoVue for the identification of sentinel lymph node (SLN) and the value of the combination of CEUS and blue dye (BD) for SLNB in patients converting from cN1 to cN0 following NAC. METHODS: Patients with cytology-proven node positive breast cancer at the initial diagnosis (stage T1-T3N1M0) from January 2018 to January 2019, underwent NAC. Patients converting from cN1 to cN0 following NAC were enrolled and randomized into two groups for SLNB: the combination method group using CEUS and BD together, and the single BD method group. Then all patients underwent complete axillary lymph node dissection (ALND) and primary breast surgery. Compared with the final pathological results, the identification rate, sensitivity, specificity, accuracy, false negative rate, negative predictive value, positive predictive value were recorded and compared between two methods. RESULTS: A total of 400 patients with stage T1-T3N1M0 disease underwent NAC between January 2018 to January 2019, among which 134 (33.5%) patients had clinically negative node confirmed by imaging after NAC and randomized into two groups. Each group included 67 cases. In the combination method group, contrast-enhanced lymphatic vessels in 66 cases of 67 were clearly visualized by US soon after the periareolar injection of SonoVue and the SLNs were accurately localized. The identification rate of the combination method was 98.5%%, which was significantly higher than 83.6% (56/67) using the single BD method. The mean numbers of SLNs identified by the combination method was higher than that by the single BD method. Compared with pathological diagnosis, sensitivity, specificity, accuracy, the positive predictive value, the negative predictive value, and the FNR of the combingation method were 84.4%, 100%, 89.4%, 100%, 75%, and 15.6%, respectively. In contrast, sensitivity, specificity, accuracy, the positive predictive value, the negative predictive value, and the FNR using single blue dye were 73.9%, 100%, 89.3%, 100%, 84.6%, and 26.1%, respectively. The FNR using the combination method was significantly lower than that using single BD. CONCLUSION: Identification of SLNs in patients converting from cN1 to cN0 following NAC by CEUS is a technically feasible. The combination of CEUS and BD is more effective than BD alone for SLNB in patients converting from cN1 to cN0 following NAC.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Meios de Contraste/uso terapêutico , Terapia Neoadjuvante/métodos , Linfonodo Sentinela/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Neoplasias da Mama/patologia , Meios de Contraste/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
8.
J Hazard Mater ; 398: 122820, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502801

RESUMO

Rivers are a significant reservoir of antibiotic resistance genes (ARGs), yet the biogeographic pattern of riverine ARGs and its underlying driving forces remain poorly understood. Here, we used metagenomic approach to investigate the spatio-temporal variation of ARGs in two adjacent sub-watersheds viz. North River (NR) and West River (WR), China. The results demonstrated that Bacitracin (22.8 % of the total ARGs), multidrug (20.7 %), sulfonamide (15.2 %) and tetracycline (10.9 %) were the dominant ARG types. SourceTracker analysis indicated that sewage treatment plants as the main source of ARGs, while animal feces mainly contributed in spreading the ARGs in the upstream of NR. Random forest and network analyses confirmed that NR was under the influence of fecal pollution. PCoA analysis demonstrated that the composition of ARGs changed along with the anthropogenic gradients, while the Raup-Crick null model showed that homogenizing selection mediated by class 1 integron intI1 resulted in stable ARG communities at whole watershed scale. Structural equation models revealed that microbial community, grassland and several non-antibiotic micropollutants may also play certain roles in influencing the distribution of ARGs. Overall, the observed deterministic formation of ARGs in riverine systems calls effective management strategies to mitigate the risks of antibiotic resistance on public health.

9.
EBioMedicine ; 56: 102777, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32485640

RESUMO

BACKGROUND: The diagnosis performance of B-mode ultrasound (US) for focal liver lesions (FLLs) is relatively limited. We aimed to develop a deep convolutional neural network of US (DCNN-US) for aiding radiologists in classification of malignant from benign FLLs. MATERIALS AND METHODS: This study was conducted in 13 hospitals and finally 2143 patients with 24,343 US images were enrolled. Patients who had non-cystic FLLs with pathological results were enrolled. The FLLs from 11 hospitals were randomly divided into training and internal validations (IV) cohorts with a 4:1 ratio for developing and evaluating DCNN-US. Diagnostic performance of the model was verified using external validation (EV) cohort from another two hospitals. The diagnosis value of DCNN-US was compared with that of contrast enhanced computed tomography (CT)/magnetic resonance image (MRI) and 236 radiologists, respectively. FINDINGS: The AUC of ModelLBC for FLLs was 0.924 (95% CI: 0.889-0.959) in the EV cohort. The diagnostic sensitivity and specificity of ModelLBC were superior to 15-year skilled radiologists (86.5% vs 76.1%, p = 0.0084 and 85.5% vs 76.9%, p = 0.0051, respectively). Accuracy of ModelLBC was comparable to that of contrast enhanced CT (both 84.7%) but inferior to contrast enhanced MRI (87.9%) for lesions detected by US. INTERPRETATION: DCNN-US with high sensitivity and specificity in diagnosing FLLs shows its potential to assist less-experienced radiologists in improving their performance and lowering their dependence on sectional imaging in liver cancer diagnosis.

10.
Int J Biol Sci ; 16(12): 2235-2247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32549768

RESUMO

The biological function of nuclear PAK4 in ERα-positive breast cancer osteolytic bone destruction remains unclear. Here, we find that the nuclear PAK4 promotes osteoclastogenesis and tumor-induced osteolysis via phosphorylating RUNX1. We show that nuclear PAK4 interacts with and phosphorylates RUNX1 at Thr-207, which induces its localization from the nucleus to the cytoplasm and influences direct interaction with SIN3A/HDAC1 and PRMT1. Furthermore, we reveal that RUNX1 phosphorylation by PAK4 at Thr-207 promotes osteolytic bone destruction via targeting downstream genes related to osteoclast differentiation and maturation. Importantly, we verify changes in RUNX1 subcellular localization when nuclear PAK4 is positive in breast cancer bone metastasis tissues. Functionally, we demonstrate that RUNX1 phosphorylation promotes osteolytic bone maturation and ERα-positive breast cancer-induced osteolytic bone damage in the mouse model of orthotopic breast cancer bone metastasis. Our results suggest PAK4 can be a therapeutic target for ERα-positive breast cancer osteolytic bone destruction.

11.
Cell Signal ; 73: 109697, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32593652

RESUMO

As the foremost common female malignancy, breast cancer (BC) poses a significant public health stumbling block. Although treatment protocols have improved over the years, the overall prognosis of BC remains unsatisfactory. Extensive investigations have taken place into long non coding RNAs (lncRNAs) pertaining to their involvement in carcinogenesis. The current study in connection with bioinformatics tools aimed to identify the myocardial infarction associated transcript (MIAT) as a BC-related differentially expressed lncRNA in an attempt to elucidate the effect of MIAT in BC cells. MIAT was initially overexpressed while DLG3 was down-regulated in BC. BC cells were subsequently treated with si-MIAT or/and si-DLG3, after which the expressions of DLG3 and the Hippo signaling pathway-related proteins were evaluated to analyze their regulatory mechanism in BC, which indicated that MIAT inhibition up-regulated DLG3 and activated the Hippo signaling pathway to suppress proliferation and promote apoptosis of BC cells. MS-PCR and RIP assays demonstrated that MIAT bound to the methylation proteins DNMT1, DNMT3A and DNMT3B, promoted the methylation of CpG islands in DLG3 promoter and inhibited the DLG3 expression. Moreover, our data suggested that DLG3 could bind to MST2 and regulate LAST1, which prevented the nuclear translocation of YAP. The in vitro results were further verified via the in vivo findings. Taken together, the central findings of our study demonstrate that MIAT silencing inhibits BC progression by means of up-regulating DLG3 via activation of the Hippo signaling pathway, highlighting a novel potential therapeutic target for the treatment of the BC.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32131523

RESUMO

Urban parks provide multiple non-material benefits to human health and well-being; measuring these "intangible" benefits mainly co-produced by the spatial interactivity between dwellers and urban parks is vital for urban green space management. This paper introduced "vitality" to measure the intangible benefits of urban parks and constructed a straightforward and spatially explicit approach to assess the park vitality based on visiting intensity and recreational satisfaction rate. Freely available data of check-in comments on parks, points-of-interest (POIs), and other multi-source data from Beijing were used to assess the urban park vitality and explore the factors influencing it from the perspectives of recreational service supply, demand, and spatial linking characteristics. We found that the urban park vitalities decreased along the urban-rural gradient. The presence of water and facility density in the parks have significant positive impacts on park vitality, and high population density nearby was a positive factor. Moreover, the external higher levels of the POI-based urban function mix and density, as well as developed public transportation, were strongly associated with greater park vitality. Our research proposed a feasible and effective method to assess the park vitality, and the findings from this study have significant implications for optimizing the spatial configuration of urban parks.


Assuntos
Parques Recreativos , Pequim , Humanos , Parques Recreativos/estatística & dados numéricos , Parques Recreativos/provisão & distribução , Satisfação Pessoal , Densidade Demográfica , Recreação , Transportes , População Urbana/estatística & dados numéricos
13.
Artigo em Inglês | MEDLINE | ID: mdl-32075039

RESUMO

It takes some time for changes to come in ecosystem services, and trade-offs occur in the process of changes. As opposed to a point in time, we use data spanning the years 2000-2005, 2005-2010, and 2010-2015 to study this research. After quantifying types of ecosystem services, this paper uses spatial correlation analysis and root-mean square deviation (RMSD) method to explore the relationships among ecosystem services and calculate the degree of spatial trade-offs (DT). Results show that the construction land increased substantially albeit at a declining rate of growth, and the degree of trade-offs (DT) increased with nontrivial differences in space. The hotspots for trade-offs are spatially aggregated in some areas but have varying patterns between ecosystem service pairs. The increasing area (IA) of construction land does not promote increased DT until the former reaches a certain threshold. With the exception of land use changes, type of industrial development is one of the key factors that influence the trade-offs of ecosystem services in the research region. We apply the models and methods used in this research to practice and discuss the practical value of our results for planners and decision makers vis-à-vis the design and instigation of appropriate development strategies.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Análise Espacial
14.
Sci Rep ; 9(1): 17277, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754121

RESUMO

Biochar amendment is a good means of mitigating methane (CH4) and nitrous oxide (N2O) emissions. However, the effects of biochar amendment on N2O and CH4 reduction in soil under rotation with different soil moisture contents is not well understood. To understand CH4 and N2O flux from soil with biochar amendment under water-unsaturated and water-saturated conditions, a field experiment was conducted in a tobacco-rice rotation field in subtropical China to investigate N2O and CH4 emissions following soil amendment with tobacco straw biochar at rates of 0, 10, 40 and 80 t·ha-1 (B0, B10, B40 and B80, respectively). N2O and CH4 emissions were monitored by a closed-chamber method in the water-unsaturated tobacco (UT) and water-saturated rice (SR) seasons during the 2015 planting season. The soil pH increased from 5.4 in the control to 6.1 in the soil amended with biochar at 80 t·ha-1 in the UT season. During both the UT and SR seasons, with biochar amendment at 40 and 80 t·ha-1, the soil bulk density (BD) decreased, while the soil organic matter (SOM) and available potassium (Av. K) contents increased. N2O flux was significantly greater in UT than in SR in the controls but decreased with the application of biochar during both the UT and SR seasons. The cumulative CH4 emission decreased with the rate of biochar application and the methanotroph pmoA gene copy number in soils and increased with the methanogenic archaea 16Sr DNA gene copy number in soils during the rice-cropping season. These results indicated that biochar amendment could decrease methanogenic archaea and increase of methanotroph pmoA gene, which are the mechanistic origin for CH4 reduction.

15.
Medicine (Baltimore) ; 98(40): e17424, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577758

RESUMO

RATIONALE: There are many difficult cases in the clinic because of the diversity of foreign bodies. The removal of a syringe cap is not so easy because there is always no hole at the closed end. PATIENT CONCERNS: A 54-year-old man suddenly developed dyspnea during his treatment in the hospital. DIAGNOSES: Foreign body in the left main bronchus. INTERVENTIONS: The foreign body was removed using fiberoptic bronchoscope together with gastroscope biopsy forceps. OUTCOMES: A repeat CT showed well inflation of left lung. LESSONS: The combined use of gastroscope biopsy forceps in trachea is more conducive to remove a foreign body similar to a syringe cap.


Assuntos
Brônquios , Broncoscopia , Corpos Estranhos/cirurgia , Gastroscopia/instrumentação , Biópsia/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade
16.
Surg Oncol ; 30: 117-121, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500773

RESUMO

PURPOSE: Multimodality treatment of soft tissue sarcoma(STS) by expert teams reportedly affords a tremendous improvement in outcome of patients. Despite advances, treatment of local unresectable recurrence remains difficult and is not standardized. We performed this retrospective study in order to assess the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treating STS patients with local unresectable recurrence. METHODS: Thirty-six STS patients with local unresectable recurrence from January 2015 to December 2016 were recruited according to the inclusion criteria. Pain rating, response rate, disease control rate, local disease progression-free survival(LPFS), progression-free survival (PFS) and overall survival(OS) were used to evaluate efficacy of HIFU treatment. RESULTS: HIFU resulted in a significant relief in pain rating, without severe side effects. According to magnetic resonance imaging(MRI), three months after HIFU treatment, response rate was 47.3% and the local disease control rate was 80.6%. Twelve months post HIFU treatment, response rate was 38.9% and the local disease control rate was 55.6%. The median LPFS, PFS and OS time for 36 patients was 13 months, 10 months and 20 months respectively. CONCLUSION: HIFU is a tolerated treatment modality with promising activity and safety in STS patients with local unresectable recurrence.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/mortalidade , Recidiva Local de Neoplasia/mortalidade , Sarcoma/mortalidade , Adolescente , Adulto , Idoso , Criança , China , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/terapia , Taxa de Sobrevida , Adulto Jovem
17.
Bull Environ Contam Toxicol ; 103(2): 308-315, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190165

RESUMO

In our study, we collected 146 surface soil samples in Xiamen City and measured the concentrations of five heavy metals (Cr, Cu, Pb, Ni, and Zn) and one metalloid (As). Multivariate statistics, geostatistics and Random Forest methods were applied to identify the potential sources and spatial variation of the six elements. The results revealed that As, Cr, and Ni originated mainly from industrial activities, and higher concentrations were found in developed areas. The amounts of Cu, Pb, and Zn in soils were mainly predetermined by soil parent material and agricultural activities. Besides, the atmospheric deposition rather than industrial activities substantially influenced the accumulation of Pb in the soils near the boundary between Tong'an and Quanzhou City, because there were few industries but many forests in this area. Because of the connections of the six elements with factor values of factor analysis, appropriate and accessible covariates could be used in co-kriging to increase the accuracies of interpolation of heavy metal and metalloid concentrations relative to that in ordinary kriging.


Assuntos
Monitoramento Ambiental/métodos , Metaloides/análise , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Agricultura , China , Cidades , Indústrias , Análise Espacial
18.
Anal Chem ; 91(13): 8229-8236, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31142114

RESUMO

Glutamate, one of the most important central excitatory neurotransmitters, plays crucial roles in nerve signal transduction and is implicated in several neurological disorders. However, no effective means has been developed for specific detection of glutamate released from primary cultured neurons. Here we present a reduced graphene oxide (RGO)-based field effect transistor (FET) biosensor functionalized with synthesized glutamate receptor for real-time monitoring of glutamate release from primary cultured rat hippocampus neurons. Metabotropic glutamate receptors (mGluR) was specifically synthesized and then immobilized on the RGO surface by 1-pyrenebutanoic acid succinimidyl ester (PASE) linker, after which target glutamate (pI = 3.22) could specifically bind to the synthesized mGluR in the neutral buffer, causing the charge density change. After the neurons were cultured on the sensing channel with a self-made liquid reservoir, the FET biosensor could discriminate glutamate in the femtomolar range in complete cell culture medium and generate encouraging results in real-time monitoring of glutamate release from primary rat hippocampus neurons. This work is the first report of specific and direct detection of glutamate molecules released from primary culture of differentiated central neurons, which may further help understand the nature of neuronal communication. Moreover, this work paves a way for the detection of electrochemically inactive small molecules released by cells.


Assuntos
Técnicas Biossensoriais/métodos , Ácido Glutâmico/metabolismo , Hipocampo/citologia , Neurônios/metabolismo , Animais , Técnicas Biossensoriais/instrumentação , Células Cultivadas , Grafite , Hipocampo/metabolismo , Ratos , Receptores de Glutamato Metabotrópico
19.
Mol Med Rep ; 19(5): 4027-4034, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942450

RESUMO

MicroRNAs (miRNAs) are non­coding RNAs of ~22 nucleotides in length, which serve an important role in numerous diseases. Asthma is a chronic airway inflammatory disease, which is the most common chronic disease among children. The role of miRNA (miR)­16 in asthma is unclear. The objective of the present study was to examine the underlying molecular mechanism of the involvement of miR­16 in asthma. A total of 72 volunteers diagnosed with asthma consented to participate in the study, of whom 52 participants were identified to be sensitive to salmeterol and 20 participants were identified to be resistant to salmeterol. Receiver operating characteristic (ROC) curve analysis was performed to compare the expression levels of serum miR­16 between the sensitive and resistant groups, and to confirm the association between the expression level of serum miR­16 and forced expiratory volume in 1 sec (FEV1). In silico analysis, a luciferase assay, reverse transcription­quantitative polymerase chain reaction analysis and western blotting were performed to elucidate the molecular mechanism underlying the role of miR­16 in asthma. ROC results demonstrated that the serum miR­16 level may function as a biomarker to predict the response to salmeterol therapy, and the miR­16 expression level displayed a significant negative correlation with FEV1. According to the in silico analysis, adrenoreceptor ß­2 (ADRB2) was a direct target of miR­16, and it was further confirmed by luciferase assay that 25 nM miR­16 mimic had an inhibitory effect on the luciferase activity of the wild­type ADRB2 3' untranslated region (UTR); the inhibitory effect on the luciferase activity of the wild­type ADRB2 3'UTR was stronger with 50 nM miR­16 mimic, and strongest with 75 nM miR­16 mimic, whereas the luciferase activity of the mutant ADRB2 3'UTR in cells was similar following treatment with 0, 25, 50 or 75 nM miR­16 mimic. miR­16 reduced the mRNA and protein expression levels of ADRB2 in a dose­dependent manner. These results identified that miR­16 may be used as a predictive biomarker of therapeutic response in asthma.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Asma/tratamento farmacológico , MicroRNAs/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Regiões 3' não Traduzidas , Adolescente , Adulto , Antagomirs/metabolismo , Área Sob a Curva , Asma/metabolismo , Asma/patologia , Criança , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/sangue , MicroRNAs/genética , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Curva ROC , Receptores Adrenérgicos beta 2/química , Receptores Adrenérgicos beta 2/genética , Xinafoato de Salmeterol/farmacologia , Xinafoato de Salmeterol/uso terapêutico , Regulação para Cima , Adulto Jovem
20.
Cancer Manag Res ; 11: 2163-2170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936748

RESUMO

Purpose: To evaluate a classification model of contrast-enhanced ultrasound (CEUS) and examine the characteristics of patients with false-negative diagnosis. Patients and methods: A retrospective secondary analysis of a multicenter trial of CEUS for breast cancer diagnosis (from August 2015 to April 2017) was undertaken. Patients (n=1,023) with Breast Imaging Reporting and Data System 4-5 lesions on B-mode ultrasound underwent CEUS. Pathological diagnoses were available from surgical or biopsy specimens for correlation. Lesion maximum diameter (LMD), distance to the papilla (DtP), distance from the superficial edge of the lesion to the skin (DtS), distance from the deep edge of the lesion to the pectoralis muscle (DtPM), and body mass index (BMI) were evaluated. Results: Median age and BMI were 48.0 and 41.2 years and 23.2 and 22.4 kg/m2 for patients with malignant and benign lesions, respectively. Overall sensitivity, specificity, and accuracy of CEUS for malignancy were 89.4%, 65.3%, and 75.8%, respectively. The patients with true-positive and false-negative diagnosis (ie, with malignant lesion) were older than those with false-positive and true-negative diagnosis (ie, with benign lesion). Patients with true-positive and false-positive diagnoses had higher BMI than patients with true-negative and false-negative diagnoses (P=0.004). Patients with true-positive and false-negative diagnoses had larger LMD and DtP, as well as smaller DtS and DtPM. Conclusion: Older age, higher BMI, larger LMD and DtP, and smaller DtS and DtPM were associated with malignant lesions on CEUS. Patients with these characteristics should undergo further imaging.

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