Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 147
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Emerg Microbes Infect ; 8(1): 1108-1121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31340720

RESUMO

Human papillomaviruses (HPV) contribute to most cervical cancers and are considered to be sexually transmitted. However, papillomaviruses are often found in cancers of internal organs, including the stomach, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. Here we show, in rabbit and mouse models, that blood infected with papillomavirus yields infections at permissive sites with detectable viral DNA, RNA transcripts, and protein products. The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections. Furthermore, we demonstrate that blood from infected mice can transmit the infection to uninfected animals. Finally, we demonstrate the presence of papillomavirus infections and virus-induced hyperplasia in the stomach tissues of animals infected via the blood. These results indicate that blood transmission could be another route for papillomavirus infection, implying that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection as well as subsequent cancers in tissues not normally associated with the viruses.

2.
Int J Stroke ; : 1747493019858777, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226919

RESUMO

OBJECTIVE: To investigate the comparative efficacy and safety of the low-dose versus standard-dose alteplase using real-world acute stroke registry data from Asian countries. METHODS: Individual participant data were obtained from nine acute stroke registries from China, Japan, Philippines, Singapore, South Korea, and Taiwan between 2005 and 2018. Inverse probability of treatment weight was used to remove baseline imbalances between those receiving low-dose versus standard-dose alteplase. The primary outcome was death or disability defined by modified Rankin Scale scores of 2 to 6 at 90 days. Secondary outcomes were symptomatic intracerebral hemorrhage and death. Generalized linear mixed models with the individual registry as a random intercept were performed to determine associations of treatment with low-dose alteplase and outcomes. RESULTS: Of the 6250 patients (mean age 66 years, 36% women) included in these analyses, 1610 (24%) were treated with low-dose intravenous alteplase. Clinical outcomes for low-dose alteplase were not significantly different to those for standard-dose alteplase, adjusted odds ratios for death or disability: 1.00 (0.85-1.19) and symptomatic intracerebral hemorrhage 0.87 (0.63-1.19), except for lower death with borderline significance, 0.77 (0.59-1.01). CONCLUSIONS: The present analyses of real-world Asian acute stroke registry data suggest that low-dose intravenous alteplase has overall comparable efficacy for functional recovery and greater potential safety in terms of reduced mortality, to standard-dose alteplase for the treatment of acute ischemic stroke.

3.
Brain ; 142(8): 2265-2275, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211368

RESUMO

The natural history of intradural spinal cord arteriovenous shunts is unknown. We performed an observational study in a consecutive patient cohort with symptomatic intradural spinal cord arteriovenous shunts who were admitted to three institutes to investigate the clinical course of this complex disease, which would provide valuable evidence to inform clinical decision-making. The clinical course of patients with symptomatic intradural spinal cord arteriovenous shunts from initial presentation to occurrence of clinical deterioration, initiation of treatment, or last follow-up was analysed. Patients with at least 1 month of observation were included in this study. Clinical onset and deterioration patterns were divided into acute and gradual. Annual and cumulative rates of clinical deterioration as well as their risk factors were analysed using Kaplan-Meier life table analysis and Cox proportional hazards model. To assess risks and benefits of treatment, post-treatment clinical courses were further assessed. Four hundred and sixty-six patients with a mean observational period of 36.9 ± 58.8 months were included; 56.7% of patients presented with acute onset, of whom 77.3% experienced spontaneous recovery. Age of onset older than 28 years, initial modified Aminoff and Logue scale of >3, mid-thoracic lesions and non-ventral lesions were independent predictors of failure for spontaneous recovery. The annual risk of general, acute and gradual clinical deterioration after onset was 30.7%, 9.9% and 17.7%, respectively. Risk of deterioration was highest in the early period after initial onset. Acute onset was the only independent risk factor [hazard ratio 1.957 (95% confidence interval, CI 1.324-2.894); P = 0.0008] of acute deterioration and gradual onset was the strongest predictor [hazard ratio 2.350 (95% CI 1.711-3.229); P < 0.0001] of the gradual deterioration among all the stratifying factors. After invasive treatment, complete obliteration was achieved in 37.9% of patients (138 of 364) and improved or stable clinical status was noted in 80.8% of patients. Forty-two patients (11.5%) experienced permanent complications. Overall post-treatment deterioration rate was 8.4%/year, and 5.3%/year if permanent complications were excluded. The natural history of symptomatic spinal cord arteriovenous shunts is poor, especially in the early period after onset, and early intervention is thus recommended. Initial onset pattern significantly affects the natural history of the lesion, which prompts a differentiated treatment strategy.

4.
Nat Commun ; 10(1): 2317, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127095

RESUMO

Linking human behavior to resting-state brain function is a central question in systems neuroscience. In particular, the functional timescales at which different types of behavioral factors are encoded remain largely unexplored. The behavioral counterparts of static functional connectivity (FC), at the resolution of several minutes, have been studied but behavioral correlates of dynamic measures of FC at the resolution of a few seconds remain unclear. Here, using resting-state fMRI and 58 phenotypic measures from the Human Connectome Project, we find that dynamic FC captures task-based phenotypes (e.g., processing speed or fluid intelligence scores), whereas self-reported measures (e.g., loneliness or life satisfaction) are equally well explained by static and dynamic FC. Furthermore, behaviorally relevant dynamic FC emerges from the interconnections across all resting-state networks, rather than within or between pairs of networks. Our findings shed new light on the timescales of cognitive processes involved in distinct facets of behavior.


Assuntos
Comportamento/fisiologia , Encéfalo/fisiologia , Modelos Neurológicos , Rede Nervosa/fisiologia , Descanso/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Conectoma/métodos , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/métodos , Fatores de Tempo , Adulto Jovem
5.
J Hypertens ; 37(10): 1991-1999, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31058800

RESUMO

OBJECTIVES: Evidence about sex differences in blood pressure (BP) at the time of acute stroke presentation is scarce. We aimed to summarize available data on sex differences in BP at the time of acute stroke presentation, including stratification by prior history of hypertension and stroke subtype. METHODS: We performed a systematic literature search across MEDLINE and Embase, from inception to 21 December 2018, to identify all population-based observational studies that reported BP at the time of acute stroke presentation. We extracted data on patient demographics, stroke-type (ischaemic or haemorrhagic), stroke severity, vascular risk factors, and SBP and DBP at the time of stroke presentation. Wherever possible, data were pooled for meta-analysis with weighted mean difference (WMD) and corresponding 95% confidence intervals (CI) using random effects meta-analysis. RESULTS: We included 128 138 stroke patients from 43 studies. Women had higher SBP at presentation than men (WMD, 1.46; 95% CI, 0.65-2.26); this difference was significant in ischaemic stroke (1.49; 0.25-2.72 mmHg), but not in intracerebral haemorrhage (0.19; -4.21 to 4.59 mmHg). Meta regression show that sex differences in SBP were consistent with increasing age, stroke severity, other comorbidities and medication history. CONCLUSION: This systematic review and meta-analysis indicates that women have higher SBP at the time of presentation with acute stroke. These differences are consistent with sex differences in hypertension patterns in older age, and may be explained by the fact that women are more likely to have a premorbid hypertension. This highlights the need for effective sex-specific blood pressure control in patients at high risk for stroke.

6.
Nucleic Acids Res ; 47(10): 5086-5099, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-30982901

RESUMO

BRCA1-associated basal-like breast cancer originates from luminal progenitor cells. Breast epithelial cells from cancer-free BRCA1 mutation carriers are defective in luminal differentiation. However, how BRCA1 deficiency leads to lineage-specific differentiation defect is not clear. BRCA1 is implicated in resolving R-loops, DNA-RNA hybrid structures associated with genome instability and transcriptional regulation. We recently showed that R-loops are preferentially accumulated in breast luminal epithelial cells of BRCA1 mutation carriers. Here, we interrogate the impact of a BRCA1 mutation-associated R-loop located in a putative transcriptional enhancer upstream of the ERα-encoding ESR1 gene. Genetic ablation confirms the relevance of this R-loop-containing region to enhancer-promoter interactions and transcriptional activation of the corresponding neighboring genes, including ESR1, CCDC170 and RMND1. BRCA1 knockdown in ERα+ luminal breast cancer cells increases intensity of this R-loop and reduces transcription of its neighboring genes. The deleterious effect of BRCA1 depletion on transcription is mitigated by ectopic expression of R-loop-removing RNase H1. Furthermore, RNase H1 overexpression in primary breast cells from BRCA1 mutation carriers results in a shift from luminal progenitor cells to mature luminal cells. Our findings suggest that BRCA1-dependent R-loop mitigation contributes to luminal cell-specific transcription and differentiation, which could in turn suppress BRCA1-associated tumorigenesis.

7.
Neuroimage ; 196: 126-141, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30974241

RESUMO

Global signal regression (GSR) is one of the most debated preprocessing strategies for resting-state functional MRI. GSR effectively removes global artifacts driven by motion and respiration, but also discards globally distributed neural information and introduces negative correlations between certain brain regions. The vast majority of previous studies have focused on the effectiveness of GSR in removing imaging artifacts, as well as its potential biases. Given the growing interest in functional connectivity fingerprinting, here we considered the utilitarian question of whether GSR strengthens or weakens associations between resting-state functional connectivity (RSFC) and multiple behavioral measures across cognition, personality and emotion. By applying the variance component model to the Brain Genomics Superstruct Project (GSP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 47% across 23 behavioral measures after GSR. In the Human Connectome Project (HCP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 40% across 58 behavioral measures, when GSR was applied after ICA-FIX de-noising. To ensure generalizability, we repeated our analyses using kernel regression. GSR improved behavioral prediction accuracies by an average of 64% and 12% in the GSP and HCP datasets respectively. Importantly, the results were consistent across methods. A behavioral measure with greater RSFC-explained variance (using the variance component model) also exhibited greater prediction accuracy (using kernel regression). A behavioral measure with greater improvement in behavioral variance explained after GSR (using the variance component model) also enjoyed greater improvement in prediction accuracy after GSR (using kernel regression). Furthermore, GSR appeared to benefit task performance measures more than self-reported measures. Since GSR was more effective at removing motion-related and respiratory-related artifacts, GSR-related increases in variance explained and prediction accuracies were unlikely the result of motion-related or respiratory-related artifacts. However, it is worth emphasizing that the current study focused on whole-brain RSFC, so it remains unclear whether GSR improves RSFC-behavioral associations for specific connections or networks. Overall, our results suggest that at least in the case for young healthy adults, GSR strengthens the associations between RSFC and most (although not all) behavioral measures. Code for the variance component model and ridge regression can be found here: https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/preprocessing/Li2019_GSR.

8.
Plant Dis ; 103(6): 1058-1067, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30958107

RESUMO

Pathogen-free stock plants are required as propagation materials in nurseries and healthy materials are needed in germplasm exchange between countries or regions through quarantine programs. In addition, plant gene banks also prefer to maintain pathogen-free germplasm collections. Shoot tip cryotherapy is a novel biotechnology method whereby cryopreservation methods are used to eradicate obligate pathogens from vegetatively propagated plants. Long-term preservation of pathogens is necessary in all types of virus-related basic research and applications such as antigen preparation for virus detection by immunology-based methods, production of plant-based vaccines, genetic transformation to produce virus-derived resistant transgenic plants, and bionanotechnology to produce nano drugs. Obligate plant pathogens such as viruses and viroids are intracellular parasites that colonize only living cells of the hosts. Therefore, their long-term preservation is difficult. Cryotreatments cannot completely eradicate the obligate pathogens that do not infect meristematic cells and certain proportions of plants recovered from cryotreatments are still pathogen-infected. Furthermore, cryotreatments often fail to eradicate the obligate pathogens that infect meristematic cells. Cryopreservation can be used for the long-term cryopreservation of the obligate plant pathogens. Thus, cryobiotechnology functions as a double-edged sword for plant pathogen eradication and cryopreservation. This review provides updated a synthesis of advances in cryopreservation techniques for eradication and cryopreservation of obligate plant pathogens.


Assuntos
Criopreservação , Vírus de Plantas , Plantas , Brotos de Planta/virologia , Plantas/virologia
9.
Environ Sci Pollut Res Int ; 26(13): 12798-12806, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887449

RESUMO

The low-low temperature electrostatic precipitator (LLT-ESP), a combination of a traditional temperature electrostatic precipitator (ESP) and a non-leakage media gas-gas exchange (MGGH), could reduce the inlet flue gas temperature below the dew point and improved the performance of the ESP. Particulate matter (PM) from the stationary sources contains filterable particulate matter (FPM) and condensable particulate matter (CPM). In this study, coal with a high ash content (coal-HA) was burned, and the emission characteristics and removal efficiencies of the particulate matter in an LLT-ESP were investigated. The standards used to test filterable and condensable PM were ISO standard 23210-2009 and U.S. EPA Method 202, respectively. The LLT-ESP was efficient in removing filterable PM, with a total filterable PM removal efficiency as high as 99.6%. The removal efficiency of filterable PM increased with increasing particulate size and decreasing imported flue gas temperature. The LLT-ESP also provided excellent removal of condensable PM with a condensable PM removal efficiency exceeding 77%. Upstream of the LLT-ESP, the concentrations of filterable PM were much higher than those of condensable PM. Downstream of the LLT-ESP, the relationship between the quantities of condensable and filterable PM reversed. To reduce the emissions of PM from coal-fired power plants, more attention should be paid to controlling condensable PM. The temperature of the flue gas upstream of the LLT-ESP played an important role in eliminating condensable PM. At lower imported flue gas temperature operation conditions, the removal efficiency of the LLT-ESP for the condensable PM and the escaping mass concentration of condensable PM increased. Among the organic fraction of the condensable PM, hydrocarbons and esters were dominant. Meanwhile, SO42- was the primary component, followed by Cl- in anions. Na+, Ca2+, and Fe3+ were the main components in metal ions. Particles with diameters ≥ 10 µm, which contained most of the Si and Al, were dominant in the fly ash collected from sections 1 and 2 of the LLT-ESP. The main particles in sections 3 and 4 were PM10, which contained the highest concentrations of Ca and Fe.


Assuntos
Cinza de Carvão/análise , Material Particulado/análise , Material Particulado/química , Centrais Elétricas , Poluentes Atmosféricos/análise , Carvão Mineral , Cinza de Carvão/química , Desenho de Equipamento , Eletricidade Estática , Temperatura Ambiente
10.
Meat Sci ; 152: 73-80, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30831540

RESUMO

It has been demonstrated that optical spectroscopy is a powerful tool for the quantitative monitoring of the main chemical components in food. However, portable spectrometer for on-site food quality assessment has rarely been reported. Here, a low-cost and portable hyperspectral scanner is developed. Utilizing this hyperspectral scanner by handheld push-broom scanning, reflectance spectra of meat samples can be obtained non-invasively and rapidly. Support vector regression (SVR) model is used to predict the pH value. The prediction accuracy rate of the model is close to 90%, and the coefficient of determination is about 0.93, which shows the feasibility of this system in on-site monitoring pH of meat.


Assuntos
Qualidade dos Alimentos , Carne Vermelha/análise , Análise Espectral/instrumentação , Animais , Concentração de Íons de Hidrogênio , Análise Espectral/métodos , Suínos
11.
Ann Neurol ; 85(5): 752-764, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30840312

RESUMO

OBJECTIVE: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. METHODS: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year. RESULTS: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004). INTERPRETATION: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764.

12.
Cancer Biother Radiopharm ; 34(5): 297-305, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901274

RESUMO

Background: Ruyiping is an effective traditional Chinese herbal medicine formula for preventing postoperative recurrence and metastasis of breast cancer. However, the exact function and underlying mechanism of Ruyiping in breast cancer remain unclear. Materials and Methods: After breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with Ruyiping, the CCK8, colony formation, wound-healing, and transwell invasion assays were used to examine cell proliferation, migration, and invasion, respectively. Flow cytometry was performed to examine the effect of Ruyiping on cell cycle distribution. Western blot was performed to examine the expression of related proteins, and the activity of MMP9 was detected using Gelatin zymography assay. Results: Ruyiping treatment significantly inhibited cell proliferation and viability of MDA-MB-231 and MDA-MB-468 cells. Ruyiping was also revealed to trigger cell cycle arrest at the G2 phase in MDA-MB-231 and MDA-MB-468 cells. Moreover, Ruyiping suppressed the migration and invasion abilities of MDA-MB-231 and MDA-MB-468 cells in vitro. Furthermore, Ruyiping blocked the activity of MMP9 in MDA-MB-231 and MDA-MB-468 cells. Additionally, western blotting showed that Ruyiping attenuated epithelial-to-mesenchymal transition (EMT) of breast cancer through downregulation of N-cadherin, Vimentin, Snail1, and Snail2 and upregulation of E-cadherin. The authors observed that the components of Ruyiping Pseudobulbus Cremastra seu pleiones polysaccharide and curcumol showed significant suppression in the growth and invasion of breast cancer cell. Conclusions: The observations of this study suggest the antitumor properties of Ruyiping in cell growth and invasion of breast cancer, which are modulated by induction of cell cycle arrest and reduction of MMP9 and EMT.

13.
Neuroimage ; 189: 804-812, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30711467

RESUMO

There is significant interest in using resting-state functional connectivity (RSFC) to predict human behavior. Good behavioral prediction should in theory require RSFC to be sufficiently distinct across participants; if RSFC were the same across participants, then behavioral prediction would obviously be poor. Therefore, we hypothesize that removing common resting-state functional magnetic resonance imaging (rs-fMRI) signals that are shared across participants would improve behavioral prediction. Here, we considered 803 participants from the human connectome project (HCP) with four rs-fMRI runs. We applied the common and orthogonal basis extraction (COBE) technique to decompose each HCP run into two subspaces: a common (group-level) subspace shared across all participants and a subject-specific subspace. We found that the first common COBE component of the first HCP run was localized to the visual cortex and was unique to the run. On the other hand, the second common COBE component of the first HCP run and the first common COBE component of the remaining HCP runs were highly similar and localized to regions within the default network, including the posterior cingulate cortex and precuneus. Overall, this suggests the presence of run-specific (state-specific) effects that were shared across participants. By removing the first and second common COBE components from the first HCP run, and the first common COBE component from the remaining HCP runs, the resulting RSFC improves behavioral prediction by an average of 11.7% across 58 behavioral measures spanning cognition, emotion and personality.

14.
Acta Histochem ; 121(3): 323-329, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30777303

RESUMO

Myostatin (MSTN) is a key negative regulator of muscle growth and development. Skeletal, cardiac, and smooth muscles were isolated from MSTN knockout (MSTN-∕-) and control mice to investigate the effect of knocking out MSTN on peroxisome proliferator-activated receptor 1 coactivator (PGC-1α)-III and fibronectin domain 5 (FNDC5) expression. Various molecular biology techniques were used to analyze the changes in PGC-1α-FNDC5 in different muscle types from MSTN-∕- mice. The expression levels of PGC-1α and FNDC5 in the skeletal, cardiac, and smooth muscles of MSTN-∕- mice differed from those in the skeletal, cardiac, and smooth muscles of normal mice. This study revealed that knocking out MSTN resulted in inconsistent PGC-1α and FNDC5 expression in specific muscles. It proved for the first time that MSTN deletion attenuated the expression of PGC-1α and FNDC5 in three different murine muscle types. MSTN deletion may have additional effects on the status ofFNDC5 expression. Further research, however, is needed to confirm this conclusion.


Assuntos
Fibronectinas/metabolismo , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Animais , Camundongos , Condicionamento Físico Animal/fisiologia , Fatores de Transcrição/metabolismo
15.
BMC Complement Altern Med ; 19(1): 48, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760265

RESUMO

BACKGROUND: Development of safe and effective chemopreventive agents is a winning strategy in reducing the morbidity and mortality of breast cancer. The current study was to investigate the mechanism-based chemopreventive potential of a Chinese herb formula Yanghe Huayan (YHHY) Decoction on the classical 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinogenesis model. METHODS: Female Sprague-Dawley rats at 42 days of age were orally administered with a human equivalent dose of YHHY Decoction at 0.02 ml/g (10 mg/ml) once daily, starting 1 wk. before and 4 wks following DMBA treatment. Mammary tumor occurrence was monitored every day. The length of time before palpable tumor is examined is defined as tumor-free survival time. High performance liquid chromatography (HPLC) analyses were adopted to identify major chemical compositions of the decoction. Following bioinformatics data mining and experimental analyses were performed to demonstrate the underlying mechanism of action. RESULTS: DMBA animals receiving YHHY Decoction exhibited a significant delay (P = 0.014) and in some animals prevention (P = 0.046) of tumor occurrence without obvious toxicity. Oncogenic myc activation was significantly suppressed in the DMBA-induced rats by the YHHY treatment. Eight major chemical compositions of the decoction were identified and were shown to interfere with multiple tumorigenic pathways simultaneously in the mammary tumors, including inducing tumor apoptosis and up-regulating pro-apoptotic protein Bax and down-regulating anti-apoptotic protein Bcl-2; suppressing abnormal cell proliferation and the MAPK/ERK, PI3K/AKT signalings; blocking neo-angiogenesis and the VEGF/KDR signaling, and inhibiting oxidative stress in the mammary tumors. CONCLUSION: The multi-components and multi-targeting properties of the YHHY Decoction support its use as a potent chemopreventive drug in breast cancer.


Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Mamárias Experimentais/prevenção & controle , Administração Oral , Animais , Antracenos/efeitos adversos , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/efeitos adversos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
16.
Lipids Health Dis ; 18(1): 37, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30709407

RESUMO

BACKGROUND: Recently, the harmful effects of frying oil on health have been gradually realized. However, as main components of frying oils, biochemical effects of total polar compounds (TPC) on a cellular level were underestimated. METHODS: The effects of total polar compounds (TPC) in the frying oil on the lipid metabolism, oxidative stress and cytotoxicity of HepG2 cells were investigated through a series of biochemical methods, such as oil red staining, real-time polymerase chain reaction (RT-PCR), cell apoptosis and cell arrest. RESULTS: Herein, we found that the survival rate of HepG2 cells treated with TPC decreased in a time and dose dependent manner, and thereby presented significant lipid deposition over the concentration of 0.5 mg/mL. TPC were also found to suppress the expression levels of PPARα, CPT1 and ACOX, elevate the expression level of MTP and cause the disorder of lipid metabolism. TPC ranged from 0 to 2 mg/mL could significantly elevate the amounts of reactive oxygen species (ROS) in HepG2 cells, and simultaneously increase the malondialdehyde (MDA) content from 21.21 ± 2.62 to 65.71 ± 4.20 µmol/mg of protein (p < 0.05) at 24 h. On the contrary, antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) respectively decreased by 0.52-, 0.56- and 0.28-fold, when HepG2 cells were exposed to 2 mg/mL TPC for 24 h. In addition, TPC could at least partially induce the apoptosis of HepG2 cells, and the transition from G0/G1 to G2 phase in HepG2 cells was impeded. CONCLUSIONS: TPC could progressively cause lipid deposition, oxidative stress and cytotoxicity, providing the theoretical support for the detrimental health effects of TPC.


Assuntos
Gorduras/farmacologia , Células Hep G2/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2/metabolismo , Temperatura Alta , Humanos , Óleo de Amendoim , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase/metabolismo , Triglicerídeos/metabolismo
17.
Cell Mol Neurobiol ; 39(2): 265-286, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30607811

RESUMO

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA contributing to protect the blood-brain barrier (BBB) after stroke. We searched for small molecules that may up-regulate MALAT1 and focused on polydatin (PD), a natural product, as a possible candidate. PD enhanced MALAT1 gene expression in rat brain microvascular endothelial cells, reducing cell toxicity and apoptosis after oxygen and glucose deprivation (OGD). These effects correlated with reduction of inflammatory factors and enhancement of expression of BBB markers. We found opposite changes after MALAT1 silencing. We determined that C/EBPß is a key transcription factor for PD-mediated MALAT1 expression. PPARγ activity is involved in MALAT1 protective effects through its coactivator PGC-1α and the transcription factor CREB. This suggests that PD activates the MALAT1/CREB/PGC-1α/PPARγ signaling pathway to protect endothelial cells against ischemia. PD administration to rats subjected to brain ischemia by transient middle cerebral artery occlusion (tMCAO) reduced cerebral infarct volume and brain inflammation, protected cerebrovascular endothelial cells and BBB integrity. These effects correlated with increased expression of MALAT1, C/EBPß, and PGC-1α. Our results strongly suggest that the beneficial effects of PD involve the C/EBPß/MALAT1/CREB/PGC-1α/PPARγ pathway, which may provide a novel therapeutic strategy for brain ischemic stroke.


Assuntos
Encéfalo/irrigação sanguínea , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Glucosídeos/uso terapêutico , Microvasos/metabolismo , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Longo não Codificante/genética , Estilbenos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Sequência de Bases , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glucosídeos/química , Glucosídeos/farmacologia , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Modelos Biológicos , RNA Longo não Codificante/metabolismo , Ratos Sprague-Dawley , Estilbenos/química , Estilbenos/farmacologia , Fatores de Tempo
18.
Biomed Pharmacother ; 110: 850-856, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557834

RESUMO

MicroRNA-542-3p (miR-542-3p) has been implicated in several cancers; however, its precise role in ovarian cancer is unclear. In this study, we found that miR-542-3p was significantly downregulated in epithelial ovarian cancer (EOC) tissues and cell lines. Functional assays showed that overexpression of miR-542-3p suppressed tumor cell proliferation, migration, and invasion in vitro, whereas miR-542-3p knockdown dramatically promoted tumor cell proliferation and invasion. An in vivo assay also revealed that miR-542-3p overexpression significantly attenuated tumor growth. Mechanistically, the gene of cyclin-dependent kinase 14 (CDK14) was identified as a novel target of miR-542-3p. CDK14 overexpression reversed the suppressive effects of miR-542-3p in ovarian cancer cells. Collectively, these results suggest that miR-542-3p functions as a tumor-suppressive miRNA in ovarian cancer by directly targeting CDK14. Our data provide novel insights into potential future treatments for patients with ovarian cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinogênese/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Proliferação de Células/fisiologia , Quinases Ciclina-Dependentes/biossíntese , MicroRNAs/biossíntese , Animais , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/genética , Feminino , Marcação de Genes , Células HEK293 , Humanos , Camundongos Nus , MicroRNAs/genética
19.
Brain ; 142(1): 23-34, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30544177

RESUMO

Brain and spinal arteriovenous malformations are congenital lesions causing intracranial haemorrhage or permanent disability especially in young people. We investigated whether the vast majority or all brain and spinal arteriovenous malformations are associated with detectable tumour-related somatic mutations. In a cohort of 31 patients (21 with brain and 10 with spinal arteriovenous malformations), tissue and paired blood samples were analysed with ultradeep next generation sequencing of a panel of 422 common tumour genes to identify the somatic mutations. We used droplet digital polymerase chain reaction to confirm the panel sequenced mutations and identify the additional low variant frequency mutations. The association of mutation variant frequencies and clinical features were analysed. The average sequencing depth was 1077 ± 298×. High prevalence (87.1%) of KRAS/BRAF somatic mutations was found in brain and spinal arteriovenous malformations with no other replicated tumour-related mutations. The prevalence of KRAS/BRAF mutation was 81.0% (17 of 21) in brain and 100% (10 of 10) in spinal arteriovenous malformations. We detected activating BRAF mutations and two novel mutations in KRAS (p.G12A and p.S65_A66insDS) in CNS arteriovenous malformations for the first time. The mutation variant frequencies were negatively correlated with nidus volumes of brain (P = 0.038) and spinal (P = 0.028) arteriovenous malformations but not ages. Our findings support a causative role of somatic tumour-related mutations of KRAS/BRAF in the overwhelming majority of brain and spinal arteriovenous malformations. This pathway homogeneity and high prevalence implies the development of targeted therapies with RAS/RAF pathway inhibitors without the necessity of tissue genetic diagnosis.10.1093/brain/awy307_video1awy307media15978667388001.


Assuntos
Malformações Arteriovenosas/genética , Encéfalo/anormalidades , Predisposição Genética para Doença/genética , Malformações do Sistema Nervoso/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Medula Espinal/anormalidades , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , Análise de Sequência de DNA/estatística & dados numéricos , Adulto Jovem
20.
ACS Synth Biol ; 7(12): 2709-2714, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30525473

RESUMO

The 5' untranslated region (5'UTR) plays a key role in post-transcriptional regulation, but interaction between nucleotides and directed evolution of 5'UTRs as synthetic regulatory elements remain unclear. By constructing a library of synthesized random 5'UTRs of 24 nucleotides in Saccharomyces cerevisiae, we observed strong epistatic interactions among bases from different positions in the 5'UTR. Taking into account these base interactions, we constructed a mathematical model to predict protein abundance with a precision of R2 = 0.60. On the basis of this model, we developed an approach to engineer 5'UTRs according to nucleotide sequence activity relationships (NuSAR), in which 5'UTRs were engineered stepwise through repeated cycles of backbone design, directed screening, and model reconstruction. After three rounds of NuSAR, the predictive accuracy of our model was improved to R2 = 0.71, and a strong 5'UTR was obtained with 5-fold higher protein abundance than the starting 5'UTR. Our findings provide new insights into the mechanism of 5'UTR regulation and  contribute to a new translational elements engineering approach in synthetic biology.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA