RESUMO
Insulin-like growth factor binding protein-3 (IGFBP-3) has previously been identified as a putative tumor suppressor gene. The present study investigated the clinical and prognostic significance of IGFBP-3 expression levels in patients with hepatocellular carcinoma (HCC). Immunohistochemistry (IHC) probing for IGFBP-3 was performed on paraffin-embedded tissue samples obtained from 120 patients with HCC, including tissue samples from 120 primary cancer sites and 50 matched adjacent non-malignant sites. Receiver-operator curve (ROC) analysis was used to determine the cut-off scores for the presence of IGFBP-3-positive tumor cells and to estimate the survival time of the patients. The threshold for marking the positive expression of IGFBP-3 was 65%, based on the area under the ROC. Positive expression of IGFBP-3 was observed in 65/120 (54.2%) of the HCC tissues, and in 36/50 (72%) of the adjacent non-malignant liver tissues. Low levels of IGFBP-3 expression were correlated with tumor size (P=0.003), tumor multiplicity (P=0.044), node (P=0.008), metastasis (P=0.001) and clinical stage (P=0.001), as well as reduced survival time (P=0.015). Using univariate survival analysis, a significant direct correlation between high and low IGFBP-3 expression levels, and patient survival time (mean survival time high IGFBP-3, 39.4 vs. low IGFBP-3, 18.7 months) was identified. Kaplan-Meier analysis demonstrated that IGFBP-3 expression levels and patients survival time were significantly correlated (P<0.001). Multivariate analysis revealed IGFBP-3 expression to be an independent parameter (P=0.003). Therefore, low levels of IGFBP-3 expression are associated with advance clinicopathological classification and may be a predictor of poor survival in patients with HCC. Furthermore, these findings suggest that IGFBP-3 may serve as an independent molecular marker for the evaluation of prognosis in patients with HCC.
RESUMO
It has been previously demonstrated that Astragalus and Paeoniae radix rubra extract (APE) had a protective effect against liver fibrosis in mice. The present study aimed to investigate the hepatoprotective effect of APE on CCl4induced hepatic fibrosis in rats. Liver fibrosis was induced in male SpragueDawley rats by intraperitoneal injection of 50% CCl4 twice a week for eight weeks. Organ coefficients, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), procollagen type III (PCIII), hydroxyproline (Hyp), glutathione (GSHPx), malondialdehyde (MDA), superoxide dismutase (SOD) and transforming growth factor ß1 (TGFß1) levels were measured in rats with hepatic fibrosis. Histopathological changes in affected livers were studied using hematoxylineosin and Masson's trichrome staining. The expression of transforming growth factorß/Smad pathway proteins, αsmooth muscle actin (αSMA), collagen I and collagen III was observed in fibrotic livers using western blot analysis. The present study observed significant reductions in serum levels of AST, ALT, HA, LN, PCIII and Hyp in APEtreated (2.6 and 5.2 g/kg) rats, indicating the significant hepatoprotective effects of APE. Furthermore, the depletion of GSHPx and SOD, in addition to the accumulation of MDA in liver tissue was suppressed by APE (2.6 and 5.2 g/kg). Pathological assessment of CCl4induced fibrotic livers revealed a significant reduction of liver injury and development of hepatic fibrosis in rats treated with APE (2.6 and 5.2 g/kg). Moreover, APE (2.6 and 5.2 g/kg) decreased the elevation of TGFß1, αSMA, collagen I and collagen III expression, inhibited Smad2/3 phosphorylation as well as elevated the expression of the TGFß1 inhibitor Smad7. These results suggested that APE may protect against liver damage and inhibit the progression of CCl4induced hepatic fibrosis. The mechanism of action of APE is hypothesized to proceed via scavenging free radicals, decreasing TGFß1 levels and blocking of the TGFß/Smad signaling pathway.
Assuntos
Astrágalo/química , Paeonia/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Actinas/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Astrágalo/metabolismo , Peso Corporal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/tratamento farmacológico , Cirrose Hepática Experimental/patologia , Masculino , Malondialdeído/sangue , Paeonia/metabolismo , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/sangueRESUMO
Previous studies have shown that Astragalus and Paeoniae Radix Rubra extract (APE) is capable of protecting against liver fibrosis in rats. The hypothesis of the present study was that APE exerts its antifibrotic effect by mediating the transforming growth factor ß (TGFß)/Smad signaling pathway. In order to investigate this hypothesis, a series of assays were designed to detect the effects of APE on cell proliferation, cell invasion and the activation of hepatic stellate cells (HSCs). In addition, the effects of APE on the TGFß/Smad signaling pathway were explored, with the aim of elucidating the underlying mechanisms. HSCs were initially isolated from normal rat liver. A number of assays were then employed in order to evaluate the effects of APE on the function of these cells. Cell proliferation was investigated using an MTT assay and cell invasion was observed with the use of transwell invasion chambers. Collagen synthesis was measured with a 3Hproline incorporation assay and expression of αsmooth muscle actin was used to determine the extent of HSC activation. Protein expression induced by TGFß1 in HSCs was investigated by western blot and immunofluorescence analyses. Plasminogen activator inhibitor type1 (PAI1) and urokinasetype plasminogen activator (uPA) transcriptional activity was measured using reverse transcription polymerase chain reaction. The results demonstrated that APE (580 µg/ml) significantly inhibited fetal bovine seruminduced cell proliferation in a dosedependent manner. Cell invasion and activation of HSCs induced by TGFß1 were disrupted by treatment with APE in a dosedependent manner. TGFß1 was observed to increase the phosphorylation of Smad2/3, while APE administered at higher doses produced inhibitory effects on Smad2/3 phosphorylation. In addition, administration of APE abrogated the TGFß1induced reduction in Smad7 expression in a dosedependent manner. The results further indicated that APE treatment not only reduced PAI1 expression, but also increased uPA expression in a dosedependent manner. In conclusion, APE exerted inhibitory effects on cell proliferation, invasion and activation of HSCs, and the mechanisms underlying these effects may involve the TGFß1/Smad pathway.
Assuntos
Astrágalo/química , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Paeonia/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Masculino , Fosforilação , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ratos , Proteínas Smad/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
Graphene-based electrical chemical vapor sensors can achieve extremely high sensitivity, whereas the comparatively slow sensing response and recovery, the research focused on only low concentration detection, have been known as drawbacks for many applications requiring rapid and high concentration detection. Here we report a novel graphene-based fiber-optic relative humidity (RH) sensor relying on fundamentally different sensing mechanism. The sensor can achieve power variation of up to 6.9 dB in high relative humidity range (70-95%), and display linear response with correlation coefficient of 98.2%, sensitivity of 0.31 dB/%RH, response speed of faster than 0.13%RH/s, and good repeatability in 75-95%RH. Theoretical analysis of sensing mechanism can explain the experimental result, and reveal the broad applying prospect of the sensor for other kinds of chemical vapor detection. This novel graphene-based optical sensor provides a beneficial complement to the existing electrical ones, and will promote the employment of graphene in chemical sensing techniques.
RESUMO
We demonstrated temperature sensing of a fiber with nanostructured cladding, which was constructed by titanium dioxide TiO2 nanoparticles self-assembled onto a side polished optical fiber (SPF). Significantly enhanced interaction between the propagating light and the TiO2 nanoparticles (TN) can be obtained via strong evanescent field of the SPF. The strong light-TN interaction results in temperature sensing with a maximum optical power variation of ~4dB in SPF experimentally for an external environment temperature varying from -7.8°C to 77.6°C. The novel temperature sensing device shows a linear correlation coefficient of better than 99.4%, and a sensitivity of ~0.044 dB/°C. The TN-based all-fiber-optic temperature sensing characteristics was successfully demonstrated, and it is compatible with fiber-optic interconnections and high potential in photonics applications.