RESUMEN
OBJECTIVE: The aim of this study was to evaluate the impact of particulate matter 2.5 (PM2.5) on liver function at the animal level and to study its impact targets. MATERIALS AND METHODS: 60 male and female BALB/c mice of SPF grade, aged 6-8 weeks, were randomly divided into four groups, with 15 mice in each, including the normal saline control group, the PM2.5 low dose group [2 µg/(100 g/d)], the PM2.5 medium dose group [8 µg/(100 g/d)] and the PM2.5 high dose group [16 µg/(100 g/d)]. Each day, 0.9% saline or PM2.5 particles were administered through the nasal route, and samples were taken after 3 weeks of continuous exposure. Hematoxylin-eosin staining (HE) was used to observe the liver damage caused by PM2.5. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by using an automatic biochemical analyzer to detect the content of liver glycogen and blood glucose. Multiple indicators were observed, including plasma tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels, oxidative stress response indicators reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) detection, RT-PCR and Western blot detection of glycogen synthase (GS), glucokinase (GK), nuclear factor erythroid 2-related factor 2 (Nrf2) expression and phosphorylation level of phospho-c-Jun N-terminal kinases (p-JNK). RESULTS: PM2.5 can cause damage to the liver by increasing PM2.5 concentrations, raising the metabolic rate of liver cells, resulting in a substantial amount of inflammatory infiltration and vacuolar degeneration of cells, and increasing the liver/body weight. TNF-α and IL-6 inflammatory factor expression increased (p<0.05). An increase in the serum ALT and AST levels were also observed. The blood glucose of mice increased, whereas the content of liver glycogen declined (p<0.05). ROS, MDA, and SOD levels all increased considerably. PM2.5 can drastically lower the expression of GS and GK, increase the expression of Nrf2, and raise the phosphorylation level of p-JNK (p<0.05). CONCLUSIONS: PM2.5 can induce oxidative stress in mouse liver through the Nrf2/JNK pathway, induce liver inflammation in mice, and inhibit glycogen synthesis.
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Factor 2 Relacionado con NF-E2 , Material Particulado , Femenino , Ratones , Masculino , Animales , Material Particulado/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Glucemia/metabolismo , Glucógeno Hepático/metabolismo , Estrés Oxidativo , Hígado/patología , Superóxido Dismutasa/metabolismoRESUMEN
Neovascularization has a critical role in the growth and metastatic spread of tumors, and involves recruitment of circulating endothelial progenitor cells (EPCs) from bone marrow. In this study, we examined whether EPCs could promote tumor angiogenesis, and found that the tumor growth was enhanced by the administration of EPCs. To test the hypothesis that genetically modified bone marrow-derived EPCs can be effective carriers of therapeutic agents to tumor sites, we conducted human interferon-beta (HuIFN-ß) gene transfection of EPCs with a virus vector in vitro. When HuIFN-ß was applied in the ex vivo culture of EPCs, HuIFN-ß-transduced EPCs achieved efficient killing of the total population of SPC-A1 cells, indicating a bystander effect was elicited by HuIFN-ß-transduced EPCs in vitro. When SCP-A1 cancer cells were coimplanted along with ex vivo cultivated EPCs subcutaneous injection in nude mice, the tumor growth was increased. However, the anti-tumor effect of interferon-beta (IFN-ß) offset the tumor-progressive character of EPCs and the tumor growth, and the vascular density of tumor tissues increased by coimplanted EPCs were decreased upon IFN-ß treatment. In addition, overall expression levels of vascular endothelial growth factor in tumor tissues were decreased upon IFN-ß treatment. Therefore, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system.
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Inhibidores de la Angiogénesis/genética , Endotelio Vascular/citología , Interferón beta/genética , Neoplasias/irrigación sanguínea , Neovascularización Patológica/terapia , Inhibidores de la Angiogénesis/metabolismo , Animales , Células Cultivadas , Factores de Crecimiento Endotelial/genética , Factores de Crecimiento Endotelial/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Interferón beta/metabolismo , Ratones , Ratones Desnudos , Neoplasias/metabolismo , Neoplasias/terapia , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Trasplante de Células Madre , Células Madre/metabolismo , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIM: To prospectively investigate the role of MR spectroscopy (MRS) and diffusion-weighted magnetic resonance imaging (DWI) in assessing vertebral marrow changes in postmenopausal women with osteoporosis. MATERIALS AND METHODS: Seventy-eight postmenopausal women (mean age 63.7+/-3.5 years; range 55-81 years), who underwent dual-energy x-ray absorptiometry of the spine, were divided into three bone density groups (24 with normal, 25 with osteopaenic, and 29 with osteoporotic) based on T score. Both MRS and DWI of the L3 vertebral body were performed to calculate the marrow fat content and apparent diffusion coefficient (ADC). The results were compared between three groups and correlated with BMD. RESULTS: Vertebral marrow fat content was significantly increased in the osteoporotic group (59.97+/-5.78%), when compared with that of the osteopaenic group (53.04+/-7.66%, p=0.001) and the normal bone density group (48.79+/-7.1%, p<0.001). ADC values in the osteoporotic, osteopaenic, and normal bone density groups were 0.39+/-0.02x10(-3)mm(2)/s, 0.41+/-0.02x10(-3)mm(2)/s, and 0.47+/-0.03x10(-3)mm(2)/s, respectively, with statistically significant difference (P<0.001). A statistically significant positive correlation between T scores and ADC existed (r=0.835, p<0.001). The vertebral marrow fat content was negatively correlated to the bone density (r=-0.639, p<0.001) and to marrow ADC (r=-0.554, p<0.001). CONCLUSION: The postmenopausal women with osteoporosis exhibited a corresponding increase in vertebral marrow fat content as the bone density decreased. Marrow fat content and ADC were related to the bone density. MRS and DWI are helpful in evaluating the bone marrow changes in postmenopausal women.
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Enfermedades de la Médula Ósea/diagnóstico , Imagen de Difusión por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Osteoporosis Posmenopáusica/diagnóstico , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Densidad Ósea/fisiología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Multidrug resistance of tumours is one of the most important factors that leads to chemotherapy failure. A multidrug-resistant breast cancer cell line, MCF-7/Taxol, was established from the drug-sensitive parent cell line MCF-7. The biological properties of MCF-7/Taxol, including its drug resistance profile and profile of paclitaxel binding proteins, were analysed and compared with the parent cell line. A number of paclitaxel binding proteins were present in MCF-7 cells but absent from MCF-7/Taxol cells, namely heat shock protein 90, actinin and dermcidin precursor. The identification of differential paclitaxel binding proteins between the multidrug-resistant MCF-7/Taxol cell line and the parent drug-sensitive cell line MCF-7 provides insight into possible mechanisms involved in resistance to these chemotherapy drugs.