RESUMO
Recent findings have shown that microRNAs play critical roles in the pathogenesis of diabetic nephropathy. miR-34c has been found to inhibit fibrosis and the epithelial-mesenchymal transition of kidney cells. However, the role of miR-34c in diabetic nephropathy has not been well studied. The current study was designed to investigate the role and potential underlying mechanism of miR-34c in regulating diabetic nephropathy. After treating podocytes with high glucose (HG) in vitro, we found that miR-34c was downregulated and that overexpression of miR-34c inhibited HG-induced podocyte apoptosis. The direct interaction between miR-34c and the 3'-untranslated region (UTR) of Notch1 and Jagged1 was validated by dual-luciferase reporter assay. Moreover, Notch1 and Jagged1 as putative targets of miR-34c were downregulated by miR-34c overexpression in HG-treated podocytes. Overexpression of miR-34c inhibited HG-induced Notch signaling pathway activation, as indicated by decreased expression of the Notch intracellular domain (NICD) and downstream genes including Hes1 and Hey1. Furthermore, miR-34c overexpression increased the expression of the anti-apoptotic gene Bcl-2, and decreased the expression of the pro-apoptotic protein Bax and cleaved Caspase-3. Additionally, the phosphorylation of p53 was also downregulated by miR-34c overexpression. Taken together, our findings suggest that miR-34c overexpression inhibits the Notch signaling pathway by targeting Notch1 and Jaggged1 in HG-treated podocytes, representing a novel and potential therapeutic target for the treatment of diabetic nephropathy.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Glucose/toxicidade , Proteínas de Membrana/efeitos dos fármacos , MicroRNAs/metabolismo , Podócitos/efeitos dos fármacos , Receptor Notch1/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Regiões 3' não Traduzidas , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Sítios de Ligação , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Transformada , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , MicroRNAs/genética , Podócitos/metabolismo , Podócitos/patologia , Receptor Notch1/genética , Receptor Notch1/metabolismo , Proteínas Serrate-Jagged , Fatores de Tempo , Transfecção , Regulação para CimaRESUMO
OBJECTIVE: to evaluate the corrosion resistance of a new titanium alloy for dental restoration in artificial saliva. METHODS: in simulated oral environment, the electrochemical behavior of a new titanium alloy (Ti-12.5Zr-3Nb-2.5Sn) for dental restoration based on the d-electron alloy design method with high elastic modulus, high mechanical and good biological safety properties was investigated together with that of Ti-6Al-4V and TA2 as control groups. The anodic polarization curve and polarization resistance of these alloys were analyzed and the element release of Ti-12.5Zr-3Nb-2.5Sn and Ti-6Al-4V alloy after immersion in artificial saliva for 1, 2, 3, 5, 7, 15 d were measured. RESULTS: polarization curve indicated that Ti-6Al-4V alloy had lower breakdown potential (0.8 V) than Ti-12.5Zr-3Nb-2.5Sn alloy did (> 2.5 V). Ti-6Al-4V alloy showed higher passivation current density (1.45 × 10(-4) - 1.09 × 10(-3) A/cm(2)) than Ti-12.5Zr-3Nb-2.5Sn alloy (3.32 × 10(-6) - 3.46 × 10(-5) A/cm(2)) and TA2(5.03 × 10(-6) - 2.65 × 10(-5) A/cm(2)) did. Polarization resistance results showed that polarization resistance volume of TA2, Ti-12.5Zr-3Nb-2.5Sn alloy and Ti-6Al-4V alloy were 371.0, 252.0, and 60.1 kΩ×cm(2) respectively. With the increasing of dipping time in artificial saliva, the ion release of Ti-12.5Zr-3Nb-2.5Sn alloy and Ti-6Al-4V alloy increased to different degrees. Ti-6Al-4V alloy always showed more ion release than Ti-12.5Zr-3Nb-2.5Sn alloy did in the experiment. CONCLUSIONS: data from this study indicated that Ti-12.5Zr-3Nb-2.5Sn alloy, as a dental restoration material, had good corrosion resistance in artificial saliva.
Assuntos
Materiais Dentários , Titânio , Ligas , Corrosão , Eletroquímica , Teste de Materiais , Saliva Artificial , Propriedades de SuperfícieRESUMO
A new titanium alloy (Ti-12.5Zr-3Nb-2.5Sn) was developed to meet the needs of clinical requirements for medical titanium alloys and improve the properties of existing titanium alloys. The as-prepared alloy was solution treated at 500 °C for 3 h in vacuum followed by water quenching. Tensile, wear and hardness tests were carried out to examine the mechanical properties of the Ti-Zr-Nb-Sn alloy. Oral mucous membrane irritation test was performed to evaluate the surface biological properties of the Ti-Zr-Nb-Sn alloy. The results suggested that the surface hardness and wear-resistant properties of the Ti-12.5Zr-3Nb-2.5Sn alloy were superior to commercially pure Ti. The oral mucous irritation test showed that all samples had no mucous membrane irritation. It indicates that Ti-12.5Zr-3Nb-2.5Sn has large potential to be used as dental restoration material.
Assuntos
Ligas Dentárias/química , Restauração Dentária Permanente/métodos , Nióbio/química , Estanho/química , Titânio/química , Zircônio/química , Ligas/química , Animais , Cricetinae , Módulo de Elasticidade , Dureza/fisiologia , Testes de Dureza , Masculino , Teste de Materiais , Mesocricetus , Microscopia Eletrônica de Varredura , Mucosa Bucal/patologia , Propriedades de Superfície , Resistência à TraçãoRESUMO
OBJECTIVE: To evaluate the effect of heat treatment and porcelain-fused-to-metal (PFM) processing on mechanical properties and microstructure of laser welding CoCr-NiCr dissimilar alloys. METHODS: Samples of CoCr-NiCr dissimilar alloys with 0.5 mm thickness were laser-welded single-side under the setting parameters of 280 V, 10 ms pulse duration. After being welded, samples were randomly assigned to three groups, 10 each. Group1 and 2 received heat treatment and PFM processing, respectively. Group 3 was control group without any treatment. Tensile strength, microstructure and element distribution of samples in the three groups were tested and observed using tensile test, metallographic examinations, scanning electron microscope (SEM), and energy dispersive spectroscopy (EDS) analysis. RESULTS: After heat treatment and PFM processing, tensile strength of the samples were (537.15 +/- 43.91) MPa and (534.58 +/- 48.47) MPa respectively, and elongation rates in Group 1 and 2 were (7.65 +/- 0.73)% and (7.40 +/- 0.45)%. Ductile structure can be found on tensile fracture surface of samples and it was more obvious in heat treatment group than in PFM group. The results of EDS analysis indicated that certain CoCr alloy diffused towards fusion zone and NiCr side after heat treatment and PFM processing. Compared with PFM processing group, the diffusion in the heat treatment group was more obvious. CONCLUSIONS: Heat treatment and PFM processing can improve the mechanical properties and microstructure of welded CoCr-NiCr dissimilar alloy to a certain degree. The improvements are more obvious with heat treatment than with porcelain treatment.
