RESUMO
Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) have been extensively reported to play a role in GC development; however, it remains unknown whether miR-153-3p participates in the nosogenesis of GC. GC tissues along with the adjacent nontumor tissues were obtained from 50 patients with GC. Moreover, we incubated human GC cell lines (SGC7901, AGS, MGC803, and BGC823) and a gastric epithelial cell line (GES-1) and then transfected BGC823 cells with miR-153-3p and DNA/SphK2 vector to determine the action of miR-153-3p and SphK2 on GC. RT-qPCR was performed to determine the levels of miR-153-3p and sphingosine kinase 2 (SphK2). The viability of BGC823 cells was measured by the CCK-8 assay, while wound healing assays and transwell assays were used to measure the migration and invasion ability of BGC823 cells. Western blotting analysis and immunohistochemistry (IHC) were conducted to evaluate the level of SphK2. The binding ability of miR-153-3p and SphK2 was determined by dual-luciferase reporter assays. The expression level of miR-153-3p was reduced in GC tissues and cells, while the SphK2 was enhanced. An increase in miR-153-3p level led to a decline in the growth and metastasis of GC cells and increased their apoptosis. Moreover, a decrease in miR-153-3p level elevated GC cells growth and metastasis, and attenuated their apoptosis. SphK2 was also corroborated as a downstream gene of miR-153-3p. Here, SphK2 expression was elevated in GC tissues and cells, indicating SphK2 might be involved in the development of GC. Rescue assays showed that miR-153-3p could reverse the effect of SphK2 on the cell growth, metastasis, and the apoptosis of GC cells. In conclusion, this study showed that miR-153-3p suppressed the growth and metastasis in GC cells by regulating SphK2, which might facilitate the search for novel biomarkers to treat GC.
Assuntos
MicroRNAs , Fosfotransferases (Aceptor do Grupo Álcool) , Neoplasias Gástricas , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Neoplasias Gástricas/patologiaRESUMO
We experimentally demonstrate a novel approach for microwave frequency measurement utilizing birefringence effect in the highly non-linear fiber (HNLF). A detailed theoretical analysis is presented to implement the adjustable measurement range and resolution. By stimulating a complementary polarization-domain interferometer pair in the HNLF, a mathematical expression that relates the microwave frequency and amplitude comparison function is developed. We carry out a proof-to-concept experiment. A frequency measurement range of 2.5-30 GHz with a measurement error within 0.5 GHz is achieved except 16-17.5 GHz. This method is all-optical and requires no high-speed electronic components.
RESUMO
We demonstrate a photonic approach to simultaneously realize a frequency-multiplied and phase-shifted microwave signal based on the birefringence effects in the high nonlinear fiber. The phase shift caused by asymmetric variations in refractive indexes of fiber between two orthogonal polarization states is introduced into two coherent harmonic of the modulated signals. By beating the phase-modulated sidebands, a frequency-multiplied microwave signal is generated and its phase can be adjusted by simply controlling the pump power. A microwave signal at doubled- or quadrupled-frequency with a full 2π phase shift is obtained over a frequency range from 10 GHz to 30 GHz. The proposed approach has the potential applications in the system with larger-broadband, higher-frequency and -data-rate system, even to handle a multi-wavelength operation.
RESUMO
AIMS: Diabetic nephropathy is a growing health concern, which is reported to be associated with inflammation. Luteolin has been explored for the treatment of some diabetic complications. Although several studies have verified the effect of luteolin on diabetic nephropathy, the mechanism by which the therapeutic effects of luteolin on diabetic nephropathy has not been established. Therefore, we aimed to investigate the effect of luteolin on diabetic nephropathy and its underlying mechanism. MAIN METHODS: We used western blot, Real-time PCR, immunofluorescence and flow cytometry to analyze the effects of luteolin on podocyte injury and NOD-like receptor family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in high glucose (HG) condition. Reactive oxygen species (ROS) generation was measured by flow cytometry and malondialdehyde (MDA) level. To investigate the potential mechanism, we examined cell apoptosis upon transfection of siNLRP3. KEY FINDINGS: We showed that luteolin treatment could protect podocyte against HG-induced cell apoptotic and mitochondrial membrane potential collapse. In addition, luteolin significantly reduced NLRP3 inflammasome formation and subsequent interleukin-1ß (IL-1ß) secretion in HG-induced MPC-5 cells. Interestingly, siNLRP3 abolished the effect of luteolin on cell apoptosis, suggesting that the anti-apoptotic effect was found to be mostly related to NLRP3 inflammasome. SIGNIFICANCE: In summary, our data demonstrated the abilities of luteolin to inhibit podocyte injury and NLRP3 inflammasome activation, which could be used in the treatment of diabetic nephropathy.
Assuntos
Apoptose/efeitos dos fármacos , Glucose/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação/prevenção & controle , Luteolina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Podócitos/efeitos dos fármacos , Animais , Células Cultivadas , Humanos , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/patologia , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Podócitos/metabolismo , Podócitos/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
Large and long-lasting cytosolic calcium surges in astrocytes have been described in cultured cells and acute slice preparations. The mechanisms that give rise to these calcium events have been extensively studied in vitro. However, their existence and functions in the intact brain are unknown. We have topically applied Fluo-4 AM on the cerebral cortex of anesthetized rats, and imaged cytosolic calcium fluctuation in astrocyte populations of superficial cortical layers in vivo, using two-photon laser scanning microscopy. Spontaneous [Ca(2+)](i) events in individual astrocytes were similar to those observed in vitro. Coordination of [Ca(2+)](i) events among astrocytes was indicated by the broad cross-correlograms. Increased neuronal discharge was associated with increased astrocytic [Ca(2+)](i) activity in individual cells and a robust coordination of [Ca(2+)](i) signals in neighboring astrocytes. These findings indicate potential neuron-glia communication in the intact brain.
Assuntos
Astrócitos/citologia , Compostos de Anilina/farmacologia , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Comunicação Celular , Células Cultivadas , Córtex Cerebral/metabolismo , Citosol/metabolismo , Eletrofisiologia , Feminino , Corantes Fluorescentes/farmacologia , Imuno-Histoquímica , Masculino , Microscopia Confocal , Microscopia de Vídeo , Modelos Biológicos , Neuroglia/metabolismo , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Xantenos/farmacologiaRESUMO
Here, we investigated whether I4, which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE-/- mice were fed a Western diet and simultaneously administered I4, glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I4. The data indicated that I4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I4, at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1ß, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I4 exerts potent inhibitory effects on atherosclerosis onset and development.
Assuntos
Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Aterosclerose/patologia , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Antígenos CD36/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Inflamação/complicações , Inflamação/tratamento farmacológico , Molécula 1 de Adesão Intercelular/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Células RAW 264.7 , Receptores Depuradores Classe E/metabolismo , Transdução de Sinais/efeitos dos fármacos , Compostos de Sulfonilureia/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Atherosclerosis attracts increasing global attention because of its morbidity and mortality. G004, as a synthetic sulfonylurea compound, has been confirmed to have anti-hyperglycaemia, anti-platelet and anti-thrombus effects. The aim of the present study was to investigate whether G004 suppress the onset and development of atherosclerosis and illuminate its probable mechanism of action. ApoE-/- mice that were fed a high-fat diet were randomly divided into five groups by weight; subsequently, they were treated with vehicle, G004, at different doses or atorvastatin once daily for 12weeks. Meanwhile, C57BL/6 mice with the same diet served as the normal controls. Then, the serum lipid profiles and histopathological damage to the liver, kidney, aortic arch and aortic root were analysed. The activation of endothelial nitric oxide synthase (eNOS) and levels of inflammatory markers were detected. Reverse cholesterol transport (RCT) was assessed in vivo by intraperitoneal injection of RAW264.7 cells that were radiolabelled with 3H-cholesterol. The results indicated that G004 ameliorated the serum lipid accumulation, atherosclerotic lesions and liver steatosis. Additionally, this compound increased the expression of SIRT1 and eNOS as well as the phosphorylation and deacetylation of eNOS in the aorta, alleviating the inflammatory state. RCT was promoted in ApoE-/- mice, which was accompanied by increased expression of SIRT1/LXRα/ABCA1/G1 in the liver, and similar results appeared in the cholesterol efflux assay in RAW264.7 cells. The results provide a strong rationale for G004 to be an efficient anti-atherosclerosis agent that improved vascular endothelial dysfunction by stimulating SIRT1/eNOS and promoted RCT by stimulating SIRT1/LXRα/ABCA1/G1.