Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Am J Obstet Gynecol ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31574291

RESUMO

BACKGROUND: The impact of maternal pre-pregnancy impaired fasting glucose on preterm birth and large for gestational age has been poorly understood. OBJECTIVES: We aimed to estimate the impact of pre-pregnancy impaired fasting glucose defined by the WHO cut-point on the risk of preterm birth and large for gestational age, and to investigate whether the WHO cut-point of impaired fasting glucose was appropriate for identifying women at the risk of preterm birth and large for gestational age among the Chinese population. STUDY DESIGN: This was a retrospective cohort study of women from the National Free Preconception Health Examination Project with singleton birth from 121 counties/districts in 21 cities of Guangdong Province, China, from 1st January 2013 to 31st December 2017. Women were included if pre-pregnancy fasting glucose was less than 7.0mmol/L. The primary outcomes were preterm birth (gestational age <37 weeks), early preterm birth (gestational age <34 weeks), large for gestational age (birth weight by gestational age >90th percentile based on the international standards in the INTERGROWTH-21st) and severe large for gestational age (birth weight by gestational age >97th percentile). We calculated the adjusted risk ratio for impaired fasting glucose, and a 1 standard deviation increase in fasting glucose. RESULTS: We included 640469 women. Of these, 31006 (4.84%) met the WHO cut-point for impaired fasting glucose, 32640 (5.10%) had preterm birth and 7201 (1.12%) had early preterm birth, 45532 (7.11%) had large for gestational age birth and 16231 (2.53%) had severe large for gestational age birth. Compared with women with normoglycaemia, women with pre-pregnancy impaired fasting glucose had a 7.0% higher risk of preterm birth (adjusted risk ratio 1.07, 95%CI 1.02-1.12), 10.0% higher risk of large for gestational age (1.10, 1.06-1.14) and 17.0% higher risk of severe large for gestational age (1.17, 1.10-1.26). No significant association of pre-pregnancy impaired fasting glucose with early preterm birth was found. The association of pre-pregnancy impaired fasting glucose with preterm birth and large for gestational age were similar in subgroups of women with various baseline characteristics. Adjusted risk ratio for preterm birth per standard deviation fasting glucose (0.7mmol/L) was 0.99 (95% CI 0.98-1.00), for early preterm birth 0.99 (0.97-1.02), for large for gestational age 1.04 (1.03-1.05) and for severe large for gestational age 1.03 (1.01-1.04). CONCLUSIONS: Our data suggest that maternal pre-pregnancy impaired fasting glucose increases the risk of preterm birth, large for gestational age and severe large for gestational age. Data also suggest that the WHO cut-point of impaired fasting glucose is too restrictive and lesser levels of fasting glucose also increase the risk of large gestational age and severe for severe gestational age in the Chinese population. Further investigation is warranted to determine whether and how counselling and interventions for women with pre-pregnancy impaired fasting glucose could reduce the risk of preterm birth and large for gestational age.

2.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664454

RESUMO

Microvesicles (MVs) were involved in the pathogenesis of many diseases, such as cardiovascular diseases and diabetes. Oxidative stress played a key role in the development and progression of diabetic nephropathy (DN). Our aim of the present study was to investigate whether high glucose (HG) could provoke MVs generation from podocytes and its potential mechanism. Mouse podocyte clone 5 (MPC-5) was stimulated by HG. The intracellular reactive oxygen species (ROS) of podocytes were measured by fluorescence microscopy with the probe of CM-H2DCFDA and MitoSOX™. Antioxidants N-Acetyl-l-cysteine (NAC) and α lipoic acid (α-LA) were used to treat podocytes after HG stimulation. The rate of podocyte apoptosis was evaluated with Annexin V-FITC by flow cytometry. NOX4 expression was examined and siRNA were performed to explore the mechanism of MVs generation. The quantities of MVs from MPC-5 cells was significantly increased (P<0.05) by 4.6-times after 30 mM glucose stimulation, accompanied with double increased apoptosis. Cellular ROS generation was increased by HG at the peak of 48 h stimulation. HG-induced MVs were significantly decreased by 52.9% after pretreatment by antioxidant NAC. Nevertheless, mitochondrial ROS in podocytes reached a peak at 4 h stimulation, but specific antioxidant α-LA had no effect on the production of MVs (P>0.05). Levels of NOX4 mRNA and protein expression were significantly up-regulated by HG (P<0.05). Podocyte-derived MVs by HG were eliminated by NOX4 siRNA. HG can provoke MVs generation from glomerular podocytes through ROS/NOX4 pathway, not from mitochondrial pathway.

3.
J Affect Disord ; 256: 117-124, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31174027

RESUMO

BACKGROUND: Recent studies have indicated that inflammatory pathways and hypothalamic-pituitary-adrenal (HPA) axis function may be responsible for the interaction between pain and depression. METHODS: Animals were examined for depressive and painful behavior following exposure to chronic unpredictable mild stress (CUMS) and chronic corticosterone (CORT) treatment. Subsequently, serum cytokines, adrenocorticotropic hormone (ACTH) and CORT were measured by enzyme-linked immunosorbent assay (ELISA). mRNA expression of cytokines in the brain were measured by quantitative PCR (qPCR). RESULTS: The present study found that both CUMS and chronic CORT treatment induced behavioral changes of depression comorbid hyperalgesia. Moreover, both the treatments increased levels of serum ACTH, CORT, and cytokines including tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1ß), interleukin 6 (IL6), and Caspase 1 (CASP1). Following CUMS, Il1ß levels were found to be elevated in all examined regions, including the raphe nuclei, thalamus, hippocampus, prefrontal cortex, and pituitary. In the raphe nuclei particularly, CUMS elevated all examined cytokine levels. Chronic CORT treatment, however, produced Il1ß elevation in the hippocampus and the pituitary, with showing elevated levels in all examined cytokines. LIMITATION: To clarify the causal relationship between behavioral changes and altered cytokine levels via either antidepressant treatment or blockage of pre-inflammatory cytokine production, further studies should be conducted. CONCLUSIONS: Despite similar behavioral consequences, hypercortisolism and peripheral inflammation, CUMS and chronic CORT treatment seem to produce differing inflammatory brain responses.

4.
Sensors (Basel) ; 19(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060312

RESUMO

In order to improve the practice in maintenance of power cables, this paper proposes a novel traveling-wave-based fault location method improved by unsupervised learning. The improvement mainly lies in the identification of the arrival time of the traveling wave. The proposed approach consists of four steps: (1) The traveling wave associated with the sheath currents of the cables are grouped in a matrix; (2) the use of dimensionality reduction by t-SNE (t-distributed Stochastic Neighbor Embedding) to reconstruct the matrix features in a low dimension; (3) application of the DBSCAN (density-based spatial clustering of applications with noise) clustering to cluster the sample points by the closeness of the sample distribution; (4) the arrival time of the traveling wave can be identified by searching for the maximum slope point of the non-noise cluster with the fewest samples. Simulations and calculations have been carried out for both HV (high voltage) and MV (medium voltage) cables. Results indicate that the arrival time of the traveling wave can be identified for both HV cables and MV cables with/without noise, and the method is suitable with few random time errors of the recorded data. A lab-based experiment was carried out to validate the proposed method and helped to prove the effectiveness of the clustering and the fault location.

5.
Psychiatry Res ; 276: 79-86, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31029038

RESUMO

Corticosterone (CORT), the main HPA-axis glucocorticoid hormone in rodents, is involved in the regulation of animal stress responses. However, the neural mechanisms underlying the effects of corticosteroids on depression are yet to be elucidated. We found that fluoxetine reversed neurite growth inhibition induced by CORT in PC12 cells, a widely used model system for neurobiological and neurotoxicological studies. Transcriptome profiling showed that 1,609 genes were up-regulated, whereas 1,764 genes were down-regulated significantly in the CORT group in comparison with the Control group. Of them, the expression of 589 DEGs was reversed after fluoxetine treatment, and genes related to cell morphogenesis, neurite growth, and immune function were involved in the neuroprotective effect of fluoxetine against CORT. Furthermore, expression of neurite growth-related genes, such as such as Calpain 2 (Capn2), vesicle-associated membrane protein 7 (Vamp7) and C-type natriuretic peptide (Cnp), altered in a brain region- or treatment-specific manner in the animal models of depression. Therefore, the interaction between stress, glucocorticoids, and neurite growth inhibition may be a candidate pathophysiology underlying major depressive disorder (MDD), and the identification of Capn2, Vamp7 and Cnp might provide insight into treatment of MDD.

6.
Sensors (Basel) ; 18(10)2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297649

RESUMO

In order to improve the practice in the operation and maintenance of high voltage (HV) cables, this paper proposes a fault location method based on the monitoring of cable sheath currents for use in cross-bonded HV cable systems. This method first analyzes the power⁻frequency component of the sheath current, which can be acquired at cable terminals and cable link boxes, using a Fast Fourier Transform (FFT). The cable segment where a fault occurs can be localized by the phase difference between the sheath currents at the two ends of the cable segment, because current would flow in the opposite direction towards the two ends of the cable segment with fault. Conversely, in other healthy cable segments of the same circuit, sheath currents would flow in the same direction. The exact fault position can then be located via electromagnetic time reversal (EMTR) analysis of the fault transients of the sheath current. The sheath currents have been simulated and analyzed by assuming a single-phase short-circuit fault to occur in every cable segment of a selected cross-bonded high voltage cable circuit. The sheath current monitoring system has been implemented in a 110 kV cable circuit in China. Results indicate that the proposed method is feasible and effective in location of HV cable short circuit faults.

7.
Metab Syndr Relat Disord ; 16(1): 13-19, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29356602

RESUMO

BACKGROUND: Our prior study showed that patients with sleep disorders had poor blood pressure (BP), glycemic control, and more severe complications. Therefore, sleep is very important for diabetic control. Our work was to investigate whether individualized diabetes sleep education significantly improve sleep quality and glycemic control in type 2 diabetic patients who sleep after midnight and potential mechanism by a randomized parallel interventional study. METHODS: T2D patients were randomly recruited to an intervention or control group. Patients received structured special diabetes sleep education program with 3-month follow-up. Pittsburg Sleep Quality Index (PSQI) was scored for each participant. Demographic data, HbA1c, biochemical, and some hormones were also examined. SPSS 13.0 was used for statistical analysis. RESULTS: One hundred patients were approached, and 45 were enrolled into our trial. Eventually, 31 patients completed the study. Patients in the intervention group greatly improved their sleep hygiene. After intervention, PSQI scores were lowered significantly (-1.48 ± 0.88 vs. -0.51 ± 0.71, P < 0.001), as well as significant reduction of HbA1c (-1.5 ± 0.55 vs. -1.11 ± 0.47, P < 0.05). Fasting plasma glucose was also lowered significantly. Homeostasis model assessment of insulin resistance was reduced significantly (-1.29 ± 0.97 vs. 1.04 ± 0.91, P < 0.01). Serum concentrations for interleukin (IL)-6, cortisol, and ghrelin were decreased significantly. Ghrelin (coefficients -0.65, P < 0.001), cortisol (coefficients -0.38, P < 0.05), and IL-6 (coefficients 0.452, P < 0.05) were correlated with HbA1c improvement. The change of ghrelin was negatively associated with the improvement of HbA1c. CONCLUSION: Diabetes sleep education could improve sleep quality, better blood glucose and BP, and decrease insulin resistance through healthier sleep hygiene. Lower serum concentration of ghrelin might be partly involved in the reduction of HbA1c.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Educação de Pacientes como Assunto/métodos , Transtornos do Sono-Vigília/terapia , Sono , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , China , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Grelina/sangue , Hemoglobina A Glicada/metabolismo , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Transtornos do Sono-Vigília/sangue , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
8.
Psychiatry Res ; 260: 428-431, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29268205

RESUMO

The Spindle- and Kinetochore-Associated (SKA) complex has been proven to be involved in many human mental behavioral disorders. Glucocorticoid, a hypothalamic-pituitary-adrenal (HPA) axis hormone, is a critical mediator of stress response in neurons. However, the underlying mechanisms of glucocorticoid's effects on human neuronal cells remain unclear. This study demonstrates that increased extracellular glucocorticoid levels significantly reduce neuronal cell SKA complex genes' expression levels, followed by altered neuronal cell viability and neurite development. The results suggest that the abnormality of this HPA-axis hormone could impact the neuronal cell functions through the alternation of SKA complex functions, which might induce cell death.


Assuntos
Proteínas Cromossômicas não Histona/genética , Glucocorticoides/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Proteínas Associadas aos Microtúbulos/biossíntese , Sistema Hipófise-Suprarrenal/metabolismo , Estresse Fisiológico/fisiologia , Animais , Relação Dose-Resposta a Droga , Expressão Gênica , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/genética , Células PC12 , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos , Estresse Fisiológico/efeitos dos fármacos
9.
Zhongguo Fei Ai Za Zhi ; 20(11): 727-731, 2017 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-29167000

RESUMO

BACKGROUND: Recently, there is no effective targeted drug for to the lung squamous carcinoma, the targeted drug for the adenocarcinoma does not benefit for the patients with squamous lung cancer, and researchers have known less targets for this type of patients. The main study herein is to screen and identify the specific key genes for the lung squamous carcinoma that will provide potential novel targets to describe pathogenesis of lung cancer. METHODS: Transcript sequence was used to detect the five pairs lung squamous carcinoma and normal lung tissues and bioinformatics was performed to investigate the differential coding genes between them and quantitative PCR was done to validate the key genes expression in lung cancer cell lines. RESULTS: The results of transcriptome sequence showed that 534 genes were up-regulated in the tumor tissues compared with the corresponding normal tissues. The top ten increased genes in the tumors were GAGE12J, SPRR3, PRAME, SPRR1A, SPRR2E, MAGEA3, SPRR1B, IL36G and TMPRSS11D. Next, we identified expression of SPRR family in lung cancer cell lines H520, GLC82, A549, H1299 and PC9. And we found higher expression of SPRR family genes in H1299 cells which metastasized to the lymph node. CONCLUSIONS: SPRR family genes are identified to be highly expressed in the lung squamous carcinoma by high throughput transcript sequencing. This SPRR family genes are associated with lymph node metastasis that provide novel idea for lung cancer therapy.
.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/genética , Idoso , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proteínas Ricas em Prolina do Estrato Córneo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Transcriptoma/genética
10.
Metab Syndr Relat Disord ; 15(10): 521-526, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29125808

RESUMO

BACKGROUND: Microvesicles (MVs) are small membrane vesicles that are derived from many different cell types by a process of exocytic budding of the plasma membrane. MVs may be associated with a higher incidence of vascular disease in diabetic patients, but the mechanism of this association is unclear. Diabetic patients also show hypercoagulability and platelet hyperaggregability. In this study, we investigated the generation and activity of high glucose (HG)-induced MVs from monocytes to elucidate the potential mechanism of such MVs in diabetes. METHODS: HG-induced MV generation from THP-1 monocytes before and after N-acetyl-L-cysteine (NAC) treatment was examined by enzyme-linked immunosorbent assay. MV activity was measured by spectrophotometry. Apoptosis and generation of reactive oxidative species (ROS) from THP-1 cells were detected by flow cytometry. Extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and P38/MAPK pathway components were also analyzed in treated monocytes. RESULTS: MVs were generated from THP-1 cells after 20 hr of exposure to HG (4.6-fold higher than untreated control cells), which was concomitant with a 3.3-fold increase in apoptosis (P < 0.01). The procoagulant activity (PCA) of the generated MVs was increased significantly by 4.1-fold (P < 0.01) relative to untreated cells. ROS levels peaked 2 hr after HG exposure. The frequency of MVs was greatly decreased after NAC treatment (P < 0.01). Both the ERK/MAPK and P38/MAPK pathway were activated after HG stimulation, whereas treatment with a P38 inhibitor decreased MV generation by 66% compared to untreated control. CONCLUSIONS: The generation of monocyte-derived MVs induced by HG was associated with PCA, concomitant with apoptosis and ROS generation. The P38/MAPK pathway was partly involved in this process as evidenced by the reduction in MV generation following treatment with a P38 inhibitor. Our results could provide insights into novel mechanisms of thrombogenicity in an HG state.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Vesículas Citoplasmáticas/efeitos dos fármacos , Glucose/antagonistas & inibidores , Glucose/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Diabetes Mellitus/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 34(3): 393-397, 2017 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-28604963

RESUMO

OBJECTIVE: To delineate the phenotypic characteristics of 22q11.2 deletion syndrome and the role of CRKL gene in the pathogenesis of cardiac abnormalities. METHODS: G-banded karyotyping, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization (FISH) were performed on a fetus with tetralogy of Fallot detected by ultrasound. Correlation between the genotype and phenotype was explored after precise mapping of the breakpoints on chromosome 22q11.2. SNP array was also performed on peripheral blood samples from both parents to clarify its origin. RESULTS: The fetus showed a normal karyotype of 46,XY. SNP array performed on fetal blood sample revealed a 749 kb deletion (chr22: 20 716 876-21 465 659) at 22q11.21, which encompassed the CRKL gene but not TBX1, HIRA, COMT and MAPK1. Precise mapping of the breakpoints suggested that the deleted region has overlapped with that of central 22q11.2 deletion syndrome. SNP array analysis of the parental blood samples suggested that the 22q11.21 deletion has a de novo origin. The presence of 22q11.21 deletion in the fetus was also confirmed by FISH analysis. CONCLUSION: Central 22q11.21 deletion probably accounts for the cardiac abnormalities in the fetus, for which the CRKL gene should be considered as an important candidate.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Cromossomos Humanos Par 22/genética , Síndrome de DiGeorge/genética , Doenças Fetais/genética , Proteínas Nucleares/genética , Adulto , Deleção Cromossômica , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/embriologia , Feminino , Doenças Fetais/diagnóstico , Genótipo , Humanos , Hibridização in Situ Fluorescente , Masculino , Fenótipo , Gravidez , Diagnóstico Pré-Natal
12.
Artigo em Inglês | MEDLINE | ID: mdl-28382278

RESUMO

The presence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the permanent integration of HBV DNA into the host genome confers the risk of viral reactivation and hepatocellular carcinoma. Nucleoside/nucleotide analogs alone have little or no capacity to eliminate replicative HBV templates consisting of cccDNA or integrated HBV DNA. Recently, CRISPR/Cas9 technology has been widely applied as a promising genome-editing tool, and HBV-specific CRISPR-Cas9 systems were shown to effectively mediate HBV cccDNA disruption. However, the integrated HBV DNA fragments are considered as important pro-oncogenic properties and it serves as an important template for viral replication and expression in stable HBV cell line. In this study, we completely excised a full-length 3,175-bp integrated HBV DNA fragment and disrupted HBV cccDNA in a stable HBV cell line. In HBV-excised cell line, the HBV cccDNA inside cells, supernatant HBV DNA, HBsAg, and HBeAg remained below the negative critical values for more than 10 months. Besides, by whole genome sequencing, we analyzed off-target effects and excluded cell contamination. It is the first time that the HBV infection has been fully eradicated in a stable HBV cell line. These findings demonstrate that the CRISPR-Cas9 system is a potentially powerful tool capable of promoting a radical or "sterile" HBV cure.


Assuntos
Sistemas CRISPR-Cas , Marcação de Genes , Vírus da Hepatite B/fisiologia , Hepatite B/microbiologia , Integração Viral , Sequência de Bases , Linhagem Celular , DNA Circular , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Replicação Viral
13.
Front Pharmacol ; 8: 142, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28386228

RESUMO

Prefrontal cortex (PFC)-dependent functions, such as executive function, explicit learning, and memory, are negatively affected in cocaine abusers and experimental animal models of cocaine treatment. However, its molecular mechanisms are less understood. In the present study, we performed transcriptome profiling of the dynamic changes in the PFC after repeated cocaine administration in mice. We found 463, 14, and 535 differentially expressed genes (DEGs) at 2 h, 24 h, and 7 days, respectively, after the withdrawal of chronic cocaine treatment. Time-series correlation analysis identified 5 clusters of statistically significant expression patterns. The expression levels of DEGs in Clusters 1 and 5 exhibited a gradual or fluctuant decrease, Cluster 2 exhibited an initial increase followed by a decrease or return to the baseline level, and Clusters 3 and 4 exhibited a fluctuant increase in the expression of DEGs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that genes related to oxidative phosphorylation, ribosomes, and neurodegenerative disorder were enriched in Cluster 1; genes related to the mitogen activated protein kinase (MAPK), transforming growth factor (TGF)-ß, insulin signaling, and circadian pathways were enriched in Cluster 2; genes related to plasticity-related pathways were enriched in Clusters 3 and 4; and genes related to the proteasome were enriched in Cluster 5. Our results suggest that maladaptive neural plasticity associated with psychostimulant dependence may be an ongoing degenerative process with dynamic changes in the gene network at different stages of withdrawal. Furthermore, it could be helpful to develop new therapeutic approaches according to different periods of abstinence.

14.
BMC Cancer ; 17(1): 140, 2017 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-28209128

RESUMO

BACKGROUND: Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-296 was found to play either oncogenic or tumor suppressive role in human cancers. However, the status of miR-296 and its function in CRC remain unknown. METHODS: The expression of miR-296 was confirmed by qRT-PCR in CRC tissues and cells, and its level was altered by corresponding miRNA vectors. Wound healing and Transwall assays were performed to detect the migration and invasion of CRC cells. The levels of proteins were measured using immunoblotting, immunohistochemistry and immunofluorescence. RESULTS: Underexpression of miR-296 was disclosed in CRC tissues and cells. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of CRC patients. In vitro experiments indicated that miR-296 inhibited CRC cell migration and invasion. Mechanically, miR-296 inhibited the epithelial-mesenchymal transition (EMT) of CRC cells. A negative correlation between miR-296 and S100A4 expression was observed in CRC tissues. Luciferase reporter assays indicated that miR-296 inversely regulated the luciferase activity of 3'-UTR of S100A4. Herein, S100A4 was found to be a downstream molecule of miR-296 in CRC. Furthermore, S100A4 mediated the anti-metastatic effects of miR-296 on EMT, migration and invasion of CRC cells. CONCLUSIONS: miR-296 functions as an anti-metastatic factor mainly by suppressing S100A4 in CRC. It potentially acts as a prognostic predictor and a drug-target for CRC patients.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Adulto , Idoso , Linhagem Celular Tumoral , Colo/química , Colo/metabolismo , Neoplasias Colorretais/química , Feminino , Técnicas de Silenciamento de Genes , Histocitoquímica , Humanos , Masculino , MicroRNAs/análise , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Reação em Cadeia da Polimerase em Tempo Real , Proteína A4 de Ligação a Cálcio da Família S100/análise , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo
15.
Nat Commun ; 8: 14041, 2017 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-28067230

RESUMO

Tumour cells secrete exosomes that are involved in the remodelling of the tumour-stromal environment and promoting malignancy. The mechanisms governing tumour exosome release, however, remain incompletely understood. Here we show that tumour cell exosomes secretion is controlled by pyruvate kinase type M2 (PKM2), which is upregulated and phosphorylated in tumours. During exosome secretion, phosphorylated PKM2 serves as a protein kinase to phosphorylate synaptosome-associated protein 23 (SNAP-23), which in turn enables the formation of the SNARE complex to allow exosomes release. Direct phosphorylation assay and mass spectrometry confirm that PKM2 phosphorylates SNAP-23 at Ser95. Ectopic expression of non-phosphorylated SNAP-23 mutant (Ser95→Ala95) significantly reduces PKM2-mediated exosomes release whereas expression of selective phosphomimetic SNAP-23 mutants (Ser95→Glu95 but not Ser20→Glu20) rescues the impaired exosomes release induced by PKM2 knockdown. Our findings reveal a non-metabolic function of PKM2, an enzyme associated with tumour cell reliance on aerobic glycolysis, in promoting tumour cell exosome release.


Assuntos
Proteínas de Transporte/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Proteínas Qb-SNARE/genética , Proteínas Qc-SNARE/genética , Hormônios Tireóideos/genética , Células A549 , Animais , Sequência de Bases , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Células HeLa , Células Hep G2 , Humanos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Proteínas Qb-SNARE/antagonistas & inibidores , Proteínas Qb-SNARE/metabolismo , Proteínas Qc-SNARE/antagonistas & inibidores , Proteínas Qc-SNARE/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Hormônios Tireóideos/metabolismo
16.
Cell Death Dis ; 8(1): e2540, 2017 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-28079894

RESUMO

Hepatocellular carcinoma (HCC) generally possesses a high resistance to chemotherapy. Given that autophagy is an important factor promoting tumor chemoresistance and HCC express low level of miR-26, we aim to investigate the functional role of miR-26 in autophagy-mediated chemoresistance of HCC. We found that chemotherapeutic drug doxorubicin (Dox) induced autophagy but decreased the level of miR-26a/b in HCC cells. Activating autophagy using rapamycin can directly downregulate the level of miR-26a/b in HCC cells. In turn, restoring the expression of miR-26a/b inhibited autophagy induced by Dox and promoted apoptosis in HCC cells. Further mechanistic study identified that miR-26a and miR-26b target ULK1, a critical initiator of autophagy, at post-transcriptional level. Results from 30 cases of patients with HCC also showed that tumor cellular levels of miR-26a and miR-26b are significantly downregulated as compared with the corresponding control tissues and negatively correlated with the protein level of ULK1 but are not correlated to the mRNA level of ULK1. Gain- and loss-of-function assay confirmed that miR-26a/b inhibited autophagic flux at the initial stage through targeting ULK1. Overexpression of miR-26a/b enhanced the sensitivity of HCC cells to Dox and promoted apoptosis via inhibiting autophagy in vitro. Using xenograft models in nude mice, we confirmed that miR-26a/b, via inhibiting autophagy, promoted apoptosis and sensitized hepatomas to Dox treatment in vivo. Our findings demonstrate for the first time that miR-26a/b can promote apoptosis and sensitize HCC to chemotherapy via suppressing the expression of autophagy initiator ULK1, and provide the reduction of miR-26a/b in HCC as a novel mechanism of tumor chemoresistance.


Assuntos
Apoptose/genética , Autofagia/genética , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/genética , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , MicroRNAs/biossíntese , RNA Mensageiro/genética , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 37(2): 509-12, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30280551

RESUMO

A rapid UV-Vis spectrophotometric method was proposed to determine the concentration of DMP in aqueous solutions. The linear concentration range of DMP solution at the range of 250~400 nm is 0.5~70 mmol·L(-1). At 275 nm, the linear fitting equation is A=0.030 7c+0.133 0 with a correlation of 0.980 9. The detection limitation is 9.46×10-5 mmol·L-1, the RSD (n=6) of the method were at the range of 0.100%~0.612%. The recovery ratio for salt solutions sample is 95%~104%. Temperature, pH, and coexisting K(+), Na(+), Mg(2+), Cl(-), Br(-), I(-), SO(2-)(4) ions do not affect the detection. The coexisting CO(2-)(3) and HCO(-)(3) ions can be eliminated with acidification. The results showed that the proposed method is simple in pretreatment process and has high accuracy and precision. It is a quick measurement method of DMP concentration in water solution, and can be used to measure DMP concentration in reverse flotation tail liquid and reverse flotation material pulp.

18.
Biotechnol Appl Biochem ; 64(6): 888-894, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27730684

RESUMO

Micro- and nanoimmunomagnetic beads (MIMBs and NIMBs) used for immunomagnetic separation (IMS) with PCR were studied for the rapid detection of Salmonella. The capture efficiency of the two different IMBs was evaluated by a conventional plate counting method, and the binding pattern was studied using scanning electron microscopy. The specificity of the IMBs was tested with Salmonella, Shigella flexneri, enterohemorrhagic Escherichia coli O157:H7, and Listeria monocytogenes. By comparing the pre-enrichment IMS and the IMS enrichment steps with a 5.5-H enrichment time, this study developed a rapid and sensitive method for the detection of Salmonella in chicken. The method was implemented by IMS enrichment and PCR with MIMBs and NIMBs, with a total analysis time of 8 H. We showed that the method was sensitive based on NIMBs with a detection limit of 10° CFU for Salmonella in 25 g of chicken.


Assuntos
Separação Imunomagnética , Reação em Cadeia da Polimerase , Salmonella/genética , Salmonella/isolamento & purificação , Animais , Galinhas , Separação Imunomagnética/instrumentação
19.
Cancer Sci ; 107(11): 1563-1571, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27581532

RESUMO

To assess the association of the programmed cell death ligand 1 (PD-L1) with cisplatin-based neo-adjuvant chemotherapy (NAC) response, we investigated the level of PD-L1 and found increased PD-L1 expression in chemo-resistant tumors compared with chemo-sensitive tumors according to RNA-Seq analysis. In a cohort of 92 patients with NAC, the positive staining of PD-L1 was correlated with TNM stage, lower sensitive-response rates and shorter overall survival rates. In another 30 paired tumor specimens pre- and post-chemotherapy, the patients with high PD-L1 expression post-chemotherapy had a worse outcome and higher stable disease rate. CD8+ tumor-infiltrating lymphocytes were found to be related to chemosensitive response and better prognosis and negative PD-L1 expression. Furthermore, in two patient-derived xenograft models and cell lines A549 and PC-9, cisplatin upregulated PD-L1 expression, and the enhancement of PD-L1 in cancer cell lines was in a drug dose-dependent manner. Moreover, the depletion of PD-L1 significantly reduced cisplatin resistance. When phosphatidylinositol 3-kinase/protein kinase B signaling was inhibited by corresponding inhibitors, PD-L1 expression was downregulated and apoptosis was upregulated in the cisplatin-treated cancer cells. These results suggest that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Terapia Neoadjuvante , Regulação para Cima/efeitos dos fármacos , Animais , Antígeno B7-H1/deficiência , Antígeno B7-H1/genética , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Sci Rep ; 6: 33082, 2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-27605442

RESUMO

The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia. Drug efficacy and safety, as outcomes, were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred, respectively. We derived pooled effect sizes expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The efficacy and safety of the drugs were ranked by cumulative ranking probabilities. Our findings show that febuxostat, benzbromarone, probenecid, pegloticase, and allopurinol were all highly effective at reducing the risk of hyperuricemia compared to placebo. Febuxostat had the best efficacy and safety compared to the other drugs. Furthermore, febuxostat 120 mg QD was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12-0.24) and safer (OR: 0.72, 95% CI: 0.56-0.91) than allopurinol.


Assuntos
Supressores da Gota/uso terapêutico , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangue , Gota/sangue , Gota/tratamento farmacológico , Humanos , Meta-Análise em Rede , Razão de Chances , Probabilidade , Ensaios Clínicos Controlados Aleatórios como Assunto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA