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1.
Toxicol Mech Methods ; : 1-16, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33467949

RESUMO

Smokeless tobacco products provide an alternative to cigarettes; however, smokeless tobacco is carcinogenic and harmful to human health. This study evaluated the toxicological effects of snus extracts and cigarette smoke total particulate matter (TPM) on human umbilical vein endothelial cells (HUVECs). Treated cells were examined for cell viability, reactive oxygen species (ROS), apoptosis, and inflammatory cytokines. Moreover, we explored the mechanism of programmed cell death induced by snus. The results showed that snus extracts significantly inhibited cell viability in a dose-dependent manner. ROS was significantly increased in treatment groups, and anti-oxidant treatment could not prevent snus extract-induced cell death. Snus extracts induced apoptosis, DNA damage, activation and cleavage of caspase-3 and caspase-8, pathway-related gene change, and interleukin (IL)-6 and IL-8 release in HUVECs. Snus extracts exposure may induce cytotoxicity, ROS generation, inflammatory cytokines release, and apoptosis or DNA damage through intrinsic and extrinsic pathways in HUVECs.

2.
J Nanobiotechnology ; 18(1): 21, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992314

RESUMO

BACKGROUND: Carbon nanoparticles (CNPs) have been reported to boost plant growth, while the mechanism that CNPs enhanced potassium uptake for plant growth has not been reported so far. RESULTS: In this study, the function that CNPs promoted potassium uptake in BY-2 cells was established and the potassium accumulated in cells had a significant correlation with the fresh biomass of BY-2 cells. The K+ accumulation in cells increased with the increasing concentration of CNPs. The K+ influx reached high level after treatment with CNPs and was significantly higher than that of the control group and the negative group treated with K+ channels blocker, tetraethylammonium chloride (TEA+). The K+ accumulation was not reduced in the presence of CNPs inhibitors. In the presence of potassium channel blocker TEA+ or CNPs inhibitors, the NKT1 gene expression was changed compared with the control group. The CNPs were found to preferentially transport K+ than other cations determined by rectification of ion current assay (RIC) in a conical nanocapillary. CONCLUSIONS: These results indicated that CNPs upregulated potassium gene expression to enhance K+ accumulation in BY-2 cells. Moreover, it was speculated that the CNPs simulated protein of ion channels via bulk of carboxyl for K+ permeating. These findings will provide support for improving plant growth by carbon nanoparticles.


Assuntos
Carbono/química , Nanopartículas/química , Nanopartículas/metabolismo , Canais de Potássio/genética , Canais de Potássio/metabolismo , Potássio/metabolismo , Aminoácidos/análise , Aminoácidos/metabolismo , Permeabilidade da Membrana Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Melhoramento Genético , Humanos , Potenciais da Membrana , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/metabolismo , Tetraetilamônio/química , Tetraetilamônio/metabolismo , Regulação para Cima/efeitos dos fármacos
3.
Transl Stroke Res ; 11(5): 967-982, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31872339

RESUMO

Peroxynitrite (ONOO-) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia-reperfusion injury. However, the roles of ONOO- in mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in ischemic brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOO- could directly mediate the activation and release of HMGB1 in ischemic brains with delayed t-PA treatment. With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO-) was positively correlated with HMGB1 level in acute ischemic stroke patients. Hemorrhagic transformation and t-PA-treated ischemic stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOO- decomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in ischemic rat brains with delayed t-PA treatment. ONOO- donor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial b.End3 cells in vitro. Those results suggest that ONOO- could activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOO- production and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in ischemic stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOO- production, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in ischemic brains. Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrhagic transformation, brain swelling, blood-brain barrier damage, neuronal apoptosis, and improved neurological outcomes in the ischemic stroke rat model with delayed t-PA treatment. In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO-/HMGB1/TLR2 signaling cascades.

4.
Int J Biol Macromol ; 138: 29-36, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302123

RESUMO

In this study, we employed multiple spectroscopic methods to analyze the effects of carbon nanoparticles (CNPs) on structure of cytochrome c (Cyt c) and mitochondrial function in plant cells. The tertiary structures of aromatic amino acid in Cyt c were not changed after addition of CNPs. Cyt c was found to be absorbed on the surfaces of CNPs in a non-linear manner and only bound Cyt c can be reduced. In addition, the binding of Cyt c was found to increase the diameter of CNPs at lower concentrations. The redox potential of Cyt c was almost not affected after treatment with CNPs. There were no obvious differences in cellular ATP after exposure to CNPs, and the mitochondrial membrane potential (MMP) was significantly decreased once the CNPs concentration exceeded 31.25 µg/mL. The levels of reactive oxygen species (ROS) also were increased in BY-2 cells. Taken together, these findings provide basis for the interactions between CNPs and Cyt c, as well as the effect of CNPs treatment on the mitochondria function in plant cells.


Assuntos
Carbono/química , Carbono/farmacologia , Citocromos c/química , Citocromos c/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas , Trifosfato de Adenosina/metabolismo , Carbono/metabolismo , Linhagem Celular , Eletroquímica , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Análise Espectral
5.
Talanta ; 201: 426-432, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122445

RESUMO

A novel hydrophilic-lipophilic balanced (HLB) solid phase extraction sorbent, microporous covalent triazine-terphenyl polymer (CTPCC-TP) was successfully synthesized and applied for the cleanup and extraction of tetracycline drugs in animal derived food samples. The specific ratio of two monomers, hydrophilic triazine and lipophilic aromatic rings, endowed the new material with hydrophilic-lipophilic balanced character, which made it capable of extracting both polar and nonpolar analytes. Prior to solid-phase extraction, food samples were extracted by McIlvaine buffer and passed through the CTPCC-TP cartridge. The experimental parameters affecting extraction efficiency, including loading, washing and elution were investigated and optimized. With the use of high-performance liquid chromatography-UV detection, a method detection limit in the range of 8.0-16.8 µg kg-1 and good linearity (22.6-1500 µg kg-1) for the determination of the tetracyclines in animal derived food samples can be achieved. The relative standard deviations (RSDs) for five replicate extractions of the tetracyclines ranged from 4.8 to 8.2%. The method recoveries for spiked tetracyclines (100 and 1000 µg kg-1) in bovine milk, egg, chicken liver samples were in the range of 81.3-98.7% with RSDs ranging from 3.9 to 7.7%, respectively, depending on both the analytes and samples. The method was suitable for the determination of tetracyclines in animal derived food samples.


Assuntos
Antibacterianos/análise , Contaminação de Alimentos/análise , Polímeros/química , Compostos de Terfenil/química , Tetraciclinas/análise , Triazinas/química , Adsorção , Animais , Bovinos , Galinhas , Cromatografia Líquida de Alta Pressão/métodos , Ovos/análise , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Fígado/química , Leite/química , Porosidade , Produtos Avícolas/análise , Extração em Fase Sólida/métodos
6.
Toxicol Mech Methods ; 29(7): 499-510, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31050318

RESUMO

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is classified as a Group 1 human carcinogen. It is metabolically activated by P450 enzymes to intermediate methylate and pyridyloxobutylate DNA, resulting in the formation of DNA adduct that is critical for the carcinogenicity of NNK. To directly and objectively examine the DNA adduct formation profiles without the complexity of factors in vivo, in the present study, five kinds of methyl DNA adducts were first identified in the incubation model of NNK established with human lung epithelial cells (BEAS-2B). The level of methyl DNA adducts and metabolites of NNK were quantitatively analyzed, respectively. With the increase of exposure time and dose, the level of methyl DNA adducts and metabolites increased. Furthermore, with the changes of the activity of P450 enzymes, which is the main enzyme regulating the α-hydroxylation of NNK, we found the levels of both methyl adducts and metabolites formed via α-hydroxylation in experimental groups showed the same trend compared with those in control group, while the metabolites formed via other pathways changed in the opposite trend. The result proves that the methyl adducts induced by NNK generate via α-hydroxylation pathway in BEAS-2B cells.


Assuntos
Carcinógenos/toxicidade , Adutos de DNA/metabolismo , Metilação de DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nitrosaminas/toxicidade , Carcinógenos/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Sistema Enzimático do Citocromo P-450 , Relação Dose-Resposta a Droga , Células Epiteliais/enzimologia , Células Epiteliais/metabolismo , Humanos , Hidroxilação , Pulmão/enzimologia , Pulmão/metabolismo , Nitrosaminas/metabolismo
7.
J Phys Condens Matter ; 30(40): 405002, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30152788

RESUMO

The 2D electron systems of SrTiO3/NdGaO3 (STO/NGO) and amorphous-LaAlO3/SrTiO3/NdGaO3 (a-LAO/STO/NGO) heterojunctions were explored. An obvious interaction between in-gap states (IGSs) and carriers was found. The IGSs can trap a large number of carriers and enhance carrier scattering. As a result of the high density of IGSs in STO, the conductivity of STO/NGO was severely weakened. However, for a-LAO/STO/NGO heterojunctions, the high carrier density can reduce the effect of IGSs through the electrostatic screening effect. The competition between IGSs and the screening effect of carriers results in an insulator-metal transition and a strange temperature dependence of carrier density. We also explored the interaction between IGSs and carriers theoretically. A mathematical description was proposed and the calculated results showed good agreement with experimental findings.

8.
Clin Cancer Res ; 24(17): 4072-4080, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29764853

RESUMO

Purpose: This large two-part, three-arm phase I study examined the safety and tolerability of CC-486 (an oral formulation of azacitidine, a hypomethylating agent) alone or in combination with the cytotoxic agents, carboplatin or nab-paclitaxel, in patients with advanced unresectable solid tumors.Patients and Methods: Part 1 (n = 57) was a dose escalation of CC-486 alone (arm C) or with carboplatin (arm A) or nab-paclitaxel (arm B). The primary endpoint was safety, MTD, and recommended part 2 dose (RP2D) of CC-486. In part 2 (n = 112), the primary endpoint was the safety and tolerability of CC-486 administered at the RP2D for each treatment arm, in tumor-specific expansion cohorts. Secondary endpoints included pharmacokinetics, pharmacodynamics, and antitumor activity of CC-486.Results: At pharmacologically active doses CC-486 in combination with carboplatin or nab-paclitaxel had a tolerable safety profile and no drug-drug interactions. The CC-486 RP2D was determined as 300 mg (every day, days 1-14/21) in combination with carboplatin (arm A) or as monotherapy (arm C); and 200 mg in the same dosing regimen in combination with nab-paclitaxel (arm B). Albeit limited by the small sample size, CC-486 monotherapy resulted in partial responses (three/eight) and stable disease (four/eight) in patients with nasopharyngeal cancer. Three of the stable disease responses lasted more than 150 days.Conclusions: CC-486 is well tolerated alone or in combination with carboplatin or nab-paclitaxel. Exploratory analyses suggest clinical activity of CC-486 monotherapy in nasopharyngeal cancer and provided the basis for an ongoing phase II clinical trial (ClinicalTrials.gov identifier: NCT02269943). Clin Cancer Res; 24(17); 4072-80. ©2018 AACR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Azacitidina/administração & dosagem , Neoplasias/tratamento farmacológico , Idoso , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/efeitos adversos , Carboplatina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Paclitaxel/administração & dosagem , Resultado do Tratamento
9.
DNA Cell Biol ; 37(3): 189-198, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29461880

RESUMO

The aim of this study is to discuss the hypothesis that expression of plasma atherosclerosis-associated microRNAs (miRNAs) in hyperhomocysteinemia (Hhcy) patients could predict the presence of atherosclerosis from different channels. Six plasma miRNAs (miR-145, miR-155, miR-222, miR-133, miR-217, and miR-30) selected for our study have been confirmed as critical gene regulators involved in atherosclerosis and can be steadily determined in plasma. Expression of the above six plasma circulating miRNAs revealed significant upregulation of two miRNAs (miR-133 and miR-217) and downregulation of three miRNAs (miR-145, miR-155, and miR-222). Six candidate miRNAs showed a significant correlation with homocysteine (Hcy) or lipid parameters. The results of this study indicated that miR-217 was further significantly upregulated in Hhcy + ATH groups than in normal control, Hhcy-, and atherosclerosis-alone (ATH) groups and it showed a significant negative correlation with Hcy and triglycerides. More specifically, miR-217 showed the most specific expression patterns in all patients with atherosclerosis (ATH and Hhcy + ATH groups), which may have been a diagnostic value for Hhcy complicated with atherosclerosis, and predicted the progress of atherosclerosis in Hhcy patients effectively.


Assuntos
Aterosclerose/sangue , Hiper-Homocisteinemia/sangue , MicroRNAs/sangue , Adulto , Aterosclerose/diagnóstico , Biomarcadores/sangue , Feminino , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/diagnóstico , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Curva ROC , Transcriptoma , Regulação para Cima
10.
Sci Rep ; 8(1): 404, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321497

RESUMO

Experimentally, we found the percentage of low valence cations, the ionization energy of cations in film, and the band gap of substrates to be decisive for the formation of two-dimensional electron gas at the interface of amorphous/crystalline oxide (a-2DEG). Considering these findings, we inferred that the charge transfer from the film to the interface should be the main mechanism of a-2DEG formation. This charge transfer is induced by oxygen defects in film and can be eliminated by the electron-absorbing process of cations in the film. Based on this, we propose a simple dipole model that successfully explains the origin of a-2DEG, our experimental findings, and some important properties of a-2DEG.

11.
Biomed Res Int ; 2017: 6705363, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29138752

RESUMO

Background: Atherosclerosis is a common inflammatory disease. Stem cell and endothelial progenitor cell treatments can improve cardiac function after myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) is a mobilisation agent, mobilising stem cells from the bone marrow to circulation in the blood. G-CSF may constitute a treatment of atherosclerosis. We have conducted meta-analysis to evaluate the current evidence for the effect of G-CSF on the progression of atherosclerosis in animal models and to provide reference for preclinical experiments and future human clinical trials of atherosclerosis treatment. Methods: We searched several databases and conducted a meta-analysis across seven articles using a random-effect model. All statistical analyses were performed using Review Manager Version 5.2 and Stata 12.0. Results: We found that G-CSF therapy was associated with reduced atherosclerotic lesion area (weighted mean difference (WMD): 7.29%; 95% confidence interval (CI): 2.06-12.52%; P = 0.006). No significant differences in total serum cholesterol (P = 0.54) and triglyceride levels (P = 0.95) were noted in G-CSF treatment groups compared with controls. Multivariable metaregression analysis revealed that the animal type (rabbit, P = 0.022) and frequency of G-CSF administration (>20, P = 0.007) impacted the atherosclerotic lesion area changes. Conclusion: The meta-analysis suggested that G-CSF treatment might inhibit the progression of atherosclerosis in animal models.


Assuntos
Aterosclerose/tratamento farmacológico , Modelos Animais de Doenças , Progressão da Doença , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Animais , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Estatística como Assunto
12.
Med Lav ; 108(5): 342-8, 2017 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-29084126

RESUMO

BACKGROUND: Fluoride bone injury affects millions of people exposed to fluoride worldwide, and has no treatment - prevention is the only solution. OBJECTIVES: A risk prediction model was developed to identify workers at high risk for fluoride bone injury in aluminum production. METHODS: We collected data from the Molecular Epidemiology Study of Fluoride Bone Injury. 120 fluoride bone injury cases and 120 controls were involved in the study. Logistic regression was used to determine variables in the risk prediction model. Predictive accuracy was validated with bootstrap method. Potential risk cut-offs was evaluated with receiver operating characteristic curve. RESULTS: Working history, urinary fluoride, osteocalcin, bone alkaline phosphatase and calcitonin receptor gene polymorphism were included in the final prediction model. The model had very good calibration and discrimination (C index=0.986; Brier score 0.014). CONCLUSIONS: Our fluoride bone injury risk prediction model performed well in the present data, and the working history, urinary fluoride, osteocalcin, bone alkaline phosphatase, and calcitonin receptor gene polymorphism were identified as predictors. The model could be used to assess the fluoride bone injury risk, and identify the susceptible workers.


Assuntos
Doenças Ósseas/induzido quimicamente , Fluoretos/toxicidade , Modelos Estatísticos , Doenças Profissionais/induzido quimicamente , Adulto , Estudos de Casos e Controles , Humanos , Medição de Risco
13.
Environ Toxicol Pharmacol ; 54: 40-47, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28672163

RESUMO

Cigarette smoke is a complex and oxidative aerosol. Previous researches on the hazards of cigarette smoke mainly focused on the adverse bioeffects induced by its condensates or gas vapor phase, which ignored the dynamic processes of smoking and the cigarette smoke aging. To overcome these disadvantages, we performed air-liquid interface exposure of whole smoke, which used native and unmodified smoke and ensured the exposure similar to physiological inhalation. Our results indicated that whole cigarette smoke induced lung epithelial cells (A549) and bronchial epithelial cells (BEAS-2B) damages in cytotoxicity assays (methyl thiazoly tetrazolium and neutral red uptake assays). In addition, A549 and BEAS-2B cells showed oxidative damages in whole smoke exposure, with concentration change of several biomarkers (reduced and oxidized glutathione, malondialdehyde, 4-hydroxyhydroxy-2-nonenal, extracellular superoxide dismutase, and 8-hydroxyl deoxyguanosine). These results indicate that whole smoke-induced oxidative stress occurs in two different kinds of cells at air-liquid interface.


Assuntos
Fumaça/efeitos adversos , Tabaco , 8-Hidroxi-2'-Desoxiguanosina , Células A549 , Aldeídos/metabolismo , Técnicas de Cultura de Células , Linhagem Celular , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Glutationa/metabolismo , Humanos , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
14.
BMC Cardiovasc Disord ; 17(1): 163, 2017 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-28633641

RESUMO

BACKGROUND: An elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients. METHODS: A total of 100 participants were enrolled and included normal control subjects (NC = 20), hyperhomocysteinaemia alone subjects (Hhcy = 25), hyperhomocysteinaemia and carotid artery atherosclerosis combined subjects (Hhcy + ATH = 30) and patients with standalone carotid artery atherosclerosis (ATH = 25). Plasma Hcy, supplementary biochemical parameters and carotid artery ultrasonography (USG) were measured in all participants. MicroRNA expression levels in the peripheral blood were calculated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The correlations of miR-143 and miR-145 with Hcy, blood lipid parameters and carotid artery atherosclerotic plaques were evaluated using Pearson's correlation coefficients. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the capacities of miR-143 and miR-145 for the detection of Hhcy and atherosclerosis patients. RESULTS: MiR-143 and miR-145 exhibited trends towards significance with stepwise decreases from the NC to Hhcy groups and then to the Hhcy + ATH and ATH groups. Similar results were observed in the carotid artery plaque group (Hhcy + ATH and ATH grups) compared with the no-plaque group (NC and Hhcy groups). The miR-143 expression level exhibited significant negative correlations with Hcy, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). The miR-145 expression level exhibited significant negative correlations with Hcy, TC, triglyceride (TG) and LDL-c. MiR-143 and miR-145 exhibited the greatest area under the curves (AUCs) (0.775 and 0.681, respectively) for the detection of every Hhcy patient, including those in the Hhcy and Hhcy + ATH groups, from among all subjects. CONCLUSION: The results indicated that the levels of atherosclerosis-associated circulating miR-143 and miR-145 are linked to Hhcy. MiR-143 may be used as a potential non-invasive biomarkers of Hhcy and thus may be helpful in predicting the progress of atherosclerosis in Hhcy patients.


Assuntos
Doenças das Artérias Carótidas/sangue , MicroRNA Circulante/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , MicroRNAs/sangue , Adulto , Área Sob a Curva , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/genética , Estudos de Casos e Controles , MicroRNA Circulante/genética , Feminino , Marcadores Genéticos , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/genética , Lipídeos/sangue , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ultrassonografia
15.
Eur Urol ; 71(2): 168-171, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27522164

RESUMO

Elevated circulating tumor cell (CTC) blood levels (≥5 cells/7.5ml) convey a negative prognosis in metastatic castration-resistant prostate cancer but their prognostic significance in patients receiving chemotherapy is uncertain. The association between CTC counts (at baseline or after treatment), overall survival (OS), and response to docetaxel with lenalidomide was evaluated in a 208-patient subset from the MAINSAIL trial, which compared docetaxel-prednisone-lenalidomide and docetaxel-prednisone-placebo in metastatic castration-resistant prostate cancer patients. Baseline CTCs were <5 cells/7.5ml blood in 87 (42%) patients and ≥5 cells/7.5ml in 121 (58%) patients. Neither tumor response nor prostate-specific antigen response correlated with baseline CTCs. However, CTC count ≥5 cells/7.5ml was significantly associated with lower OS (hazard ratio: 3.23, p = 0.0028). Increases in CTCs from <5 cells/7.5ml to ≥5 cells/7.5ml after three cycles were associated with significantly shorter OS (hazard ratio: 5.24, p=0.025), whereas CTC reductions from ≥5 cells/7.5ml to <5 cells/7.5ml were associated with the best prognosis (p=0.003). PATIENT SUMMARY: Our study in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy, with or without lenalidomide, showed that patient survival was best predicted by circulating tumor cell count at the start of treatment. A rising circulating tumor cell count after three cycles of therapy predicted poor survival, while a decline predicted good survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Células Neoplásicas Circulantes/patologia , Prednisona/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Talidomida/análogos & derivados , Idoso , Docetaxel , Humanos , Lenalidomida , Masculino , Prognóstico , Análise de Sobrevida , Talidomida/administração & dosagem
16.
Sci Rep ; 6: 21176, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26880204

RESUMO

Restenosis or occlusion after vascular procedures is ascribed to intimal hyperplasia. Transforming growth factor (TGF)-ß1 is involved in recruitment of mesenchymal stem cells (MSCs) following arterial injury, and its release from latent TGF-binding protein by matrix metalloproteinase (MMP)-14-induced proteolysis contributes to neointima formation. However, the relationship between MMP-14 and TGF-ß1 activation in restenosis is unknown. This study investigated the relationship using a rat model of balloon-induced injury. Rats were assigned to vehicle-, SB431542 (SB)-, or recombinant human (rh)TGF-ß1-treated groups and examined at various time points after balloon-induced injury for expression of TGF-ß1/Smad signalling pathway components, MMP-14 and MSCs markers including Nestin, CD29, and Sca1(+)CD29(+)CD11b/c(-)CD45(-). Intimal hyperplasia was reduced in SB- and rhTGF-ß1-treated rats. The expression of TGF-ß1, TGF-ß1RI, and Smad2/3 was decreased, but the levels of phosphorylated Smad2/3 were higher in SB-treated rats than vehicle-treated after 7 days to 14 days. rhTGF-ß1 administration decreased the expression of TGF-ß1/Smad pathway proteins, except for TGF-ß1RI. Nestin and CD29 expression and the number of Sca1(+)CD29(+)CD11b(-)CD45(-) cells were reduced, whereas MMP-14 expression was increased after SB431542 and rhTGF-ß1 administration. These results suggest that TGF-ß1/Smad signalling and MMP-14 act to recruit MSCs which differentiate to vascular smooth muscle cells and mesenchymal-like cells that participate in arterial repair/remodelling.


Assuntos
Metaloproteinase 14 da Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/metabolismo , Animais , Movimento Celular , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Humanos , Imuno-Histoquímica , Células-Tronco Mesenquimais/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo , Neointima/patologia , Fenótipo , Ratos , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Remodelação Vascular , Lesões do Sistema Vascular/patologia
17.
Inhal Toxicol ; 28(2): 89-94, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26865272

RESUMO

To accurately estimate the risk of inhaling cigarette smoke containing toxic chemicals, it is important that the distribution of these chemicals is accurately measured in cigarette smoke aerosol particles of various sizes. In this study, a single-channel smoking machine was directly coupled to an electrical low-pressure impactor. The particles of mainstream cigarette smoke were collected using 12 polyester films, and the particulate matter (PM) was characterized. Nicotine, tobacco-specific N-nitrosamines (TSNAs, including NNN, NAT, NAB, and NNK), polycyclic aromatic hydrocarbons (PAHs, including benzo(a)pyrene (BaP), benzo(a)anthracene, and chrysene), and heavy metals (including Cr, As, Cd, and Pb) present in the particles of different sizes were analyzed by GC, HPLC-MS/MS, GC/MS, or ICP-MS, respectively. The results demonstrated that the nicotine, TSNAs, PAHs, and heavy metals in mainstream cigarette smoke were dispersed over a particle size ranging from 0.1 µm to 2.0 µm, and the concentration of these toxic chemicals initially increased and then decreased the particle size grew. The distribution of nicotine was uniform for the PM in the size ranges of less than 0.1 µm, 0.1-1.0 µm, and 1.0-2.0 µm, TSNAs and heavy metals in particles of less 0.1 µm were more abundant, and PAHs in fine particles were also more abundant.


Assuntos
Tamanho da Partícula , Material Particulado/química , Fumaça/análise , Produtos do Tabaco/análise , Metais Pesados/química , Nicotina/química
18.
Sensors (Basel) ; 17(1)2016 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28042855

RESUMO

For multi-sensor integrated systems, such as the mobile mapping system (MMS), data fusion at sensor-level, i.e., the 2D-3D registration between an optical camera and LiDAR, is a prerequisite for higher level fusion and further applications. This paper proposes a line-based registration method for panoramic images and a LiDAR point cloud collected by a MMS. We first introduce the system configuration and specification, including the coordinate systems of the MMS, the 3D LiDAR scanners, and the two panoramic camera models. We then establish the line-based transformation model for the panoramic camera. Finally, the proposed registration method is evaluated for two types of camera models by visual inspection and quantitative comparison. The results demonstrate that the line-based registration method can significantly improve the alignment of the panoramic image and the LiDAR datasets under either the ideal spherical or the rigorous panoramic camera model, with the latter being more reliable.

19.
Bioconjug Chem ; 27(2): 302-8, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26284503

RESUMO

Fluorogenic sensors capable of spatiotemporally detecting Fe(2+) in biological systems are highly valuable in the study of iron biology. Toward this end, a new "off-on" Fe(2+)-selective fluorescent probe has been developed by incorporating an Fe(2+)-induced N-O cleavage of acylated hydroxylamine moiety into the naphthalimide fluorophore. The probe displays facile response (within 15 min) and good selectivity toward Fe(2+) with >27-fold enhancement of fluorescence intensity and high sensitivity of as low as 0.5 µM with a noticeable 3-fold fluorescence enhancement. These features of the probe have been transformed into in the convenient detection of endogenous, basal level of labile Fe(2+) pools in living cells. Furthermore, we have demonstrated the capacity of the probe for the studies of important Fe(2+) related biological functions. It can respond to the Zn(2+)-induced Fe(2+) flux, an important event observed in stroke, and facilely detect the elevated level of Fe(2+) in the brain tissue of a rat undergoing ischemic stroke at the ischemic site.


Assuntos
Encéfalo/metabolismo , Corantes Fluorescentes/química , Ferro/análise , Naftalimidas/química , Imagem Óptica , Acidente Vascular Cerebral/metabolismo , Zinco/análise , Animais , Encéfalo/patologia , Fluorescência , Corantes Fluorescentes/metabolismo , Ferro/metabolismo , Masculino , Naftalimidas/metabolismo , Imagem Óptica/métodos , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologia , Zinco/metabolismo
20.
J Huazhong Univ Sci Technolog Med Sci ; 35(5): 712-715, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26489627

RESUMO

Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway. Both of these processes form a feedback circuit which is a key link in skeletal fluorosis. In this study, an osteoblast-osteoclast co-culture model in vitro was developed to illustrate the mechanism of skeletal fluorosis. With the increase of fluoride concentration, the expression level of Sema4D was decreased and TGF-ß1 was increased continuously. OPG/RANKL mRNA level, however, increased gradually. On the basis of that, the inhibition of Sema4D/Plexin-B1/RhoA/ROCK signaling pathway caused by fluoride promoted the level of TGF-ß1 and activated the proliferation of osteoblasts. In addition, osteroprotegerin (OPG) secreted by osteoblasts was up-regulated by fluoride. The competitive combination of OPG and RANKL was strengthened and the combination of RANKL and RANK was hindered. And then the differentiation and maturation of osteoclasts were inhibited, and bone absorption was weakened, leading to skeletal fluorosis.


Assuntos
Antígenos CD/metabolismo , Fluoretos/farmacologia , Proteínas Ativadoras de GTPase/metabolismo , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/metabolismo , Semaforinas/metabolismo , Animais , Antígenos CD/genética , Proliferação de Células/efeitos dos fármacos , Retroalimentação Fisiológica , Feto , Proteínas Ativadoras de GTPase/genética , Regulação da Expressão Gênica no Desenvolvimento , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/genética , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/genética , Ratos , Receptor Ativador de Fator Nuclear kappa-B/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Receptores de Superfície Celular/genética , Semaforinas/genética , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo
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