RESUMO
BACKGROUND: Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. Here, the effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated. METHODS: Rat ASMCs were cultured with or without a neutralizing antibody to the receptor for advanced glycation end-products (RAGE), a potential receptor for S100A8 protein. Purified recombinant rat S100A8 protein was then added into the cultured cells, and the proliferation of ASMCs induced by PDGF was detected by colorimetric-based WST-8 assay and ampedance-based xCELLigence proliferation assay. The expression levels of RAGE in ASMCs were analyzed using western blotting assay. RESULTS: Results showed that exogenous S100A8 inhibited the PDGF-induced proliferation of rat ASMCs in a dose-dependent manner with the maximal effect at 1 µg/ml in vitro. Furthermore, when ASMCs was pre-treated with anti-RAGE neutralizing antibody, the inhibitory effect of S100A8 on PDGF-induced proliferation was significantly suppressed. In addition, neither the treatment with S100A8 or PDGF alone nor the pre-treatment with rS100A8 followed by PDGF stimulation affected the expression levels of RAGE. CONCLUSIONS: Our study demonstrated that S100A8 inhibits PDGF-induced ASMCs proliferation in a manner dependent on membrane receptor RAGE.
Assuntos
Calgranulina A/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/agonistas , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Animais , Células Cultivadas , RatosRESUMO
AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine. In this study we examined the correlation between MDR1, TBXA2R, PLA2G7, PEAR1 genetic polymorphisms and platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. METHODS: A total of 283 ischemic stroke patients receiving 100 mg aspirin for 7 d were genotyped for polymorphisms in MDR1 C3435T, TBXA2R (rs1131882), PLA2G7 (rs1051931, rs7756935), and PEAR1 (rs12566888, rs12041331). The platelet aggregation response was measured using an automatic platelet aggregation analyzer and a commercially available TXB2 ELISA kit. RESULTS: Thirty-three patients (11.66%) were insensitive to aspirin treatment. MDR1 3435TT genotype carriers, whose arachidonic acid (AA) or adenosine diphosphate (ADP)-induced platelet aggregation was lower than that of CC+CT genotype carriers, were less likely to suffer from aspirin resistance (odds ratio=0.421, 95% CI: 0.233-0.759). The TBXA2R rs1131882 CC genotype, which was found more frequently in the aspirin-insensitive group (81.8% vs 62.4%) than in the sensitive group, was identified as a risk factor for aspirin resistance (odds ratio=2.712, 95% CI: 1.080-6.810) with a higher level of AA-induced platelet aggregation. Due to the combined effects of PLA2G7 rs1051931 and rs7756935, carriers of the AA-CC haplotype had a higher level of ADP-induced platelet aggregation, and were at considerably higher risk of aspirin resistance than noncarriers (odds ratio=8.233, 95% CI: 1.590-42.638). CONCLUSION: A considerable portion (11.66%) of Chinese ischemic stroke patients are insensitive to aspirin treatment, which may be correlated with the MDR1 C3435T, TBXA2R (rs1131882), and PLA2G7 (rs1051931-rs7756935) polymorphisms.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Receptores de Superfície Celular/genética , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Acidente Vascular Cerebral/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Povo Asiático , Isquemia Encefálica/sangue , Isquemia Encefálica/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/genética , Tromboxano B2/biossíntese , Tromboxano B2/sangue , Falha de TratamentoRESUMO
A novel BINOL-based ratiometric fluorescent sensor (R2) is presented, which can selectively respond to Zn(2+) over Cd(2+) and other metal ions with fluorescence enhancement in aqueous solution. The R2 was successfully applied in the imaging of Zn(2+) in living cells. Additionally, the in situ generated R2-Zn(II) ensemble could further serve as a probe to distinguish histidine from other amino acids via a displacement mode.
Assuntos
Corantes Fluorescentes/síntese química , Histidina/análise , Naftóis/síntese química , Água/análise , Zinco/análise , Células HeLa , Histidina/metabolismo , Humanos , Ligação Proteica/fisiologia , Soluções/análise , Soluções/metabolismo , Água/metabolismo , Zinco/metabolismoRESUMO
Zinc blende, sphericity, monodisperse, high luminescence ZnSe quantum dots (QDs) were synthesized by a one-step mild hydrothermal route with Zn and Se dissolved in aqueous NaOH as the source material. The structure and the morphology of the sample were examined by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The results indicated that the products were cubic blende ZnSe ranging from 3.2 to 4.5 nm in size. TEM images showed that the QDs have very good dispersibility and distribution. The characteristic features of the absorption and photoluminescence spectra of ZnSe quantum dots were studied at room temperature. Compared with the bulk ZnSe, the absorption edges and luminescent peaks of ZnSe QDs were blue shifted to higher energies due to the quantum confinement effect. Photoluminescence at ultraviolet excitation showed the strong emission at 390 nm related to the higher excitonic states. ZnSe QDs exhibiting photoluminescence line widths as narrow as 40-60 nm. Meanwhile, we simply explored the theoretical mechanism of luminescence in ZnSe QDs and analogized the relation of various point defect concentrations of ZnSe.
RESUMO
There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than ß2-agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces pulmonary resistance in both ovalbumin- and house dust mite-induced asthma in mice. TSG12 induces RhoA phosphorylation, thereby inactivating the RhoA-ROCK-MYPT1-MLC pathway and causing ASMCs relaxation. TSG12 is more effective than ß2-agonists in relaxing human ASMCs and pulmonary resistance with potential clinical advantages. These results suggest that TSG12 could be a promising therapeutic approach for treating asthma.
Assuntos
Asma/tratamento farmacológico , Asma/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/agonistas , Proteínas dos Microfilamentos/genética , Simulação de Acoplamento Molecular , Proteínas Musculares/agonistas , Proteínas Musculares/genéticaRESUMO
BACKGROUND: Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. Here, the effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated. METHODS: Rat ASMCs were cultured with or without a neutralizing antibody to the receptor for advanced glycation end-products (RAGE), a potential receptor for S100A8 protein. Purified recombinant rat S100A8 protein was then added into the cultured cells, and the proliferation of ASMCs induced by PDGF was detected by colorimetric-based WST-8 assay and ampedance-based xCELLigence proliferation assay. The expression levels of RAGE in ASMCs were analyzed using western blotting assay. RESULTS: Results showed that exogenous S100A8 inhibited the PDGF-induced proliferation of rat ASMCs in a dose- dependent manner with the maximal effect at 1 µg/ml in vitro. Furthermore, when ASMCs was pre-treated with anti-RAGE neutralizing antibody, the inhibitory effect of S100A8 on PDGF-induced proliferation was significantly suppressed. In addition, neither the treatment with S100A8 or PDGF alone nor the pre-treatment with rS100A8 followed by PDGF stimulation affected the expression levels of RAGE. CONCLUSIONS: Our study demonstrated that S100A8 inhibits PDGF-induced ASMCs proliferation in a manner dependent on membrane receptor RAGE.
Assuntos
Animais , Ratos , Fator de Crescimento Derivado de Plaquetas/agonistas , Miócitos de Músculo Liso/efeitos dos fármacos , Calgranulina A/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Células CultivadasRESUMO
OBJECTIVE: To investigate the prevalence of tooth erosion of Xuzhou city's children. METHODS: The stratified, cluster and random sampling methods were performed. The prevalence of tooth erosion of 1,219 5-year-old children and 786 12-year-old children in Xuzhou city were examined by one qualified dentist. The results of clinical examination were recorded by schedule table. The risk factors of tooth erosion were investigated by questionnaire and analyzed by Logistic regression model. RESULTS: In 5-year-old children group, the prevalence of tooth erosion was 10.91%. In 12-year-old children group, the prevalence of tooth erosion was 22.14%. The ranking of tooth erosion were mostly class 1 and class 2. The tooth erosions of class 3 and above were rare. The odds rations for tooth erosion were: Acidic fruits, 1.120; acidophilous milk, 1.062; sport drinks, 1.159; carbonated drinks, 1.151; fruit juice, 1.187; drinking acidic drinks or acidophilous milk before sleeping, 6.102; gastroesophageal reflux disease, 2.311; vitamin C, 1.565; supply chalybeate, 1.598. CONCLUSION: The prevalence of tooth erosions in Xuzhou is extensive. Oral health education and drink and food guidance should be strengthened. The amount and frequency of intake of acidic food and drink should be reduced to promote oral health.
Assuntos
Comportamento Alimentar , Erosão Dentária , Bebidas Gaseificadas , Criança , China , Esmalte Dentário , Feminino , Humanos , Masculino , Prevalência , Fatores de RiscoRESUMO
Skeletal desmoplastic fibroma is an intraosseous neoplasm that is recognized as a very scare benign tumor. It has a propensity for locally aggressive behavior and local recurrence. The aim of this article is to report a case of skeletal desmoplastic fibroma in right mandible of a 4-year-old boy. The patient was found to have a large skeletal desmoplastic fibroma in right mandible, which was resected by surgical intervention. The defect was successfully restored with a titanium plate. In the report, the etiopathogenisis, pathological, radiographic features, clinical diagnosis, therapy and prognosis of skeletal desmoplastic fibroma were diccussed.