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1.
Huan Jing Ke Xue ; 44(12): 6541-6550, 2023 Dec 08.
Artículo en Chino | MEDLINE | ID: mdl-38098382

RESUMEN

To accurately assess the health benefits of the coal-to-electricity policy during the heating period in the Beijing-Tianjin-Hebei(BTH) Region, the premature deaths caused by PM2.5 before and after the implementation of the coal-to-electricity policy during the heating period in each district and county of the BTH Region were estimated, and the corresponding health loss values were calculated using the willingness to pay method. The results showed that the implementation of the coal-to-electricity policy in the BTH Region brought 1745 cases(95% CI:1443-1907) of health benefits and 2.38 billion yuan(95% CI:1.45-3.06) in economic benefits. In Beijing, Tianjin, and Hebei there were 495 cases(95% CI:436-554), 296 cases(95% CI:238-354), and 954 cases(95% CI:693-1076) of health benefits, respectively. The economic benefits were 0.35 billion yuan(95% CI:0.30-0.39), 0.33 billion yuan(95% CI:0.27-0.40), and 1.70 billion yuan(95% CI:0.88-2.28), respectively, accounting for 0.01%, 0.02%, and 0.04% of GDP in each region. The number of premature deaths due to COPD, LC, ALRI, IHD, and STROKE decreased by 187 cases(95% CI:165-224), 318 cases(95% CI:178-458), 193 cases(95% CI:115-204), 506 cases(95% CI:232-780), and 542 cases(95% CI:463-621), respectively. Areas with relatively high environmental PM2.5 concentrations and concentrated population-intensive pollution emissions can achieve significant health and economic benefits.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Beijing , Contaminantes Atmosféricos/análisis , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis , Material Particulado/análisis , Carbón Mineral/análisis , Monitoreo del Ambiente , Políticas , China
2.
Environ Sci Pollut Res Int ; 30(26): 69205-69220, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37138126

RESUMEN

In this study, a lactic acid bacterium, Enterococcus faecium, was found to prevent CaCO3 precipitation through its metabolism. On analysis of all stages of E. faecium growth, static jar tests demonstrated that stationary phase E. faecium broth possessed the highest inhibition efficiency of 97.3% at a 0.4% inoculation dosage, followed by the decline and log phases with efficiencies of 90.03% and 76.07%, respectively. Biomineralization experiments indicated that E. faecium fermented the substrate to produce organic acid, which resulted in modulation of the pH and alkalinity of the environment and thus inhibited CaCO3 precipitation. Surface characterization techniques indicated that the CaCO3 crystals precipitated by the E. faecium broth tended to be significantly distorted and formed other organogenic calcite crystals. The scale inhibition mechanisms were revealed by untargeted metabolomic analysis on log and stationary phase E. faecium broth. In total, 264 metabolites were detected, 28 of which were differential metabolites (VIP ≥ 1 and p < 0.05). Of these, 15 metabolites were upregulated in stationary phase broth, and 13 metabolites were downregulated in log phase broth. Metabolic pathway analysis suggested that improved glycolysis and the TCA cycle were the main reasons for enhancement of the antiscaling performance of E. faecium broth. These findings have significant implications for microbial metabolism-induced CaCO3 scale inhibition.


Asunto(s)
Enterococcus faecium , Enterococcus faecium/química , Metabolómica
3.
Environ Sci Pollut Res Int ; 30(8): 20833-20848, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36260227

RESUMEN

In this study, the corrosion behavior of Q235 carbon steel (CS) under a Bacillus cereus (B. cereus) inoculum in simulated cooling water was evaluated. The weight loss study proved B. cereus inoculum possessed anticorrosion efficiencies of 92.84% and 73.88% for 3-day and 14-day rotation tests, respectively. The electrochemical measurements indicated that the added B. cereus inoculum increased the charge transfer resistance and reduced corrosion current density. B. cereus cells with strong biofilm-forming capacity were able to adhere onto the Q235 CS surface to form compact biofilms and cause biomineralization. Surface characterization analysis demonstrated that the presence of the B. cereus inoculum reduced the amount of Fe2O3 and simultaneously increased the amount of CaCO3 in corrosion products. The corrosion inhibition mechanisms of the B. cereus inoculum involve forming biofilm, generating a biomineralized layer, and consuming dissolved oxygen. Thus, B. cereus inoculum provides a biological strategy for industrial cooling water anticorrosion application.


Asunto(s)
Bacillus cereus , Acero , Acero/química , Agua , Corrosión , Carbono , Anaerobiosis , Biopelículas
4.
Water Sci Technol ; 85(6): 1904-1919, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35358078

RESUMEN

In this study, six strains of microbial agents were investigated as environmently friendly scale and corrosion inhibitors for industrial cooling water applications. The static jar tests along with characterization methods were applied to evaluate the scale inhibition performance. Results showed that under a concentration of 240 mg/L, the nitrobacteria, denitrobacteria and Lactobacillus agents reached high CaCO3 scale inhibition efficiencies of 83, 82, and 86% respectively. Characterization methods indicated the deposited crystals morphologies were modified and the crystals peak intensities were lowered. In addition, weight loss measurements, electrochemical measurements, surface characterization analyses were conducted to study the corrosion inhibition performances and mechanisms. It was found that at 40 °C, Bacillus cereus agent with 200 mg/L possessed the highest corrosion inhibition efficiency of 60.11% at 3 d, together with the second-lowest current density of 13.0 µA cm-2 at 12 d. The corrosion inhibition mechanisms were attributed to biofilm accumulation and biomineralization on Q235 CS surfaces to form protective film. The results suggested microbial agents have promising potential as environmently friendly scale and corrosion inhibitors for industrial cooling water applications.


Asunto(s)
Biopelículas , Agua , Frío , Corrosión , Transición de Fase
5.
Water Sci Technol ; 85(5): 1500-1521, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35290228

RESUMEN

During the operation of the circulating cooling water system, inorganic scale deposition may cause technical problems, such as reduction of heat transfer efficiency in cooling systems and obstruction of pipes. In the industry, chemicals are often used as scale inhibitors in scale deposition control, antiscalants popular in industry are generally phosphorus and nitrogen-containing chemicals, which may lead to eutrophication. However, increasing environmental concern and discharge limitations have guided antiscalants to move toward biodegradability, nontoxicity and cost-effectiveness. This paper reviews current research on the application of using bio-materials as scale inhibitors, including proteins and amino acids, polysaccharides, plant extracts, microbial reagents, and microbiological products. The non-bioaccumulation, low cost, readily biodegradability and sustainably available characters promote the development of green-scale inhibitor chemistry.


Asunto(s)
Purificación del Agua , Agua , Calor
6.
Adv Mater ; 34(20): e2110123, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35291046

RESUMEN

Catalytic oxidation of NO and Hg0 is a crucial step to eliminate multiple pollutants from emissions from coal-fired power plants. However, traditional catalysts exhibit low catalytic activity and poor sulfur resistance due to low activation ability and poor adsorption selectivity. Herein, a single-atom Fe decorated N-doped carbon catalyst (Fe1 -N4 -C), with abundant Fe1 -N4 sites, based on a Fe-doped metal-organic framework is developed to oxidize NO and Hg0 . The results demonstrate that the Fe1 -N4 -C has ultrahigh catalytic activity for oxidizing NO and Hg0 at low and room temperature. More importantly, Fe1 -N4 -C exhibits robust sulfur resistance as it preferably adsorbs reactants over sulfur oxides, which has never been achieved before with traditional catalysts. Furthermore, SO2 boosts the catalytic oxidation of NO over Fe1 -N4 -C through accelerating the circulation of active sites. Density functional theory calculations reveal that the Fe1 -N4 active sites result in a low energy barrier and high adsorption selectivity, providing detailed molecular-level understanding for its excellent catalytic performance. This is the first report on NO and Hg0 oxidation over single-atom catalysts with strong sulfur tolerance. The outcomes demonstrate that single-atom catalysts are promising candidates for catalytic oxidation of NO and Hg0 enabling cleaner coal-fired power plant operations.

7.
Cardiovasc Eng Technol ; 10(2): 329-343, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30725434

RESUMEN

PURPOSE: This study aims to investigate the effects and the molecular mechanism of cyclosporin A (CsA) against oxidative stress injury in cultured neonatal rat cardiomyocytes. METHODS: Bax/Bcl-2, cl-casp-9/casp-9, cl-casp-3/casp-3, and iNOS/ß-actin ratios and p-IκB and IκB levels were analyzed by western blot. IL-1ß and TNF-α levels were analyzed by ELISA. RESULTS: CsA effectively improved the cell viability and reduced the extracellular lactate dehydrogenase release in cardiomyocytes after H2O2-induced oxidative damage. CsA significantly increased the superoxide dismutase activity, glutathione production, and catalase activity but decreased the malonaldehyde level. CsA treatment considerably reduced the H2O2-induced intracellular generation of reactive oxygen species, mitochondrial dysfunction, and release of cytochrome c. CsA could act against H2O2-induced ATP reduction, TCA cycle enzymes, mitochondrial complex I enzyme, and complex V enzyme in cardiomyocytes. CsA significantly decreased the Bax/Bcl-2 ratio, cl-casp-9/casp-9, and cl-casp-3/casp-3 in a concentration-dependent manner. CsA also remarkably reduced the cleaved PARP level and DNA fragmentation. NF-κB was closely related to oxidative stress injury. CsA inhibited NF-κB activation, thereby preventing the upregulation of IL-1ß, TNF-α, iNOS, and intracellular NO release. CONCLUSIONS: CsA protected cardiomyocytes against H2O2-induced cell injury. Hence, CsA may be developed as a candidate drug to prevent or treat myocardial ischemia reperfusion injury.


Asunto(s)
Antioxidantes/farmacología , Ciclosporina/farmacología , Miocitos Cardíacos/efectos de los fármacos , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Células Cultivadas , Citoprotección , Metabolismo Energético/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Mediadores de Inflamación/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
8.
Water Sci Technol ; 80(9): 1763-1773, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32039908

RESUMEN

A biological method was developed for reusing urban reclaimed water in circulating cooling water systems (CCWS), in which the compound microorganism preparation (CMP) mainly included nitrobacteria, Bacillus subtilis, photosynthetic bacteria and Thiobacillus denitrificans, was used to control the scaling, corrosion and biofouling of CCWS. The abundant carbon, nitrogen and phosphorus in urban reclaimed water met the needs of microbial growth. Compared with chemical agents, CMP had the advantages of high efficiency, no additional chemicals and being more economical. The research results showed that CMP improved water quality and decreased ammonia nitrogen (NH3-N) and chemical oxygen demand (COD). The concentration ratio of CCWS reached 3.87 using CMP. The corrosion inhibition rate of CMP and the removal rate on biofouling achieved 99.69% and 22.21%, respectively. The mechanisms of CMP to control scaling, corrosion and biofouling were discussed, and the surface characteristics and chemical compositions of corrosion products and biofouling were analyzed.


Asunto(s)
Incrustaciones Biológicas , Purificación del Agua , Amoníaco , Análisis de la Demanda Biológica de Oxígeno , Nitrógeno , Agua
9.
J Air Waste Manag Assoc ; 69(2): 234-245, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30396327

RESUMEN

Method 30B and the Ontario Hydro Method (OHM) were used to sample the mercury in the flue gas discharged from the seven power plants in Guizhou Province, southwest China. In order to investigate the mercury migration and transformation during coal combustion and pollution control process, the contents of mercury in coal samples, bottom ash, fly ash, and gypsum were measured. The mercury in the flue gas released into the atmosphere mainly existed in the form of Hg°. The precipitator shows a superior ability to remove Hgp (particulate mercury) from flue gas. The removal efficiency of Hg2+ by wet flue gas desulfurization (WFGD) was significantly higher than that for the other two forms of mercury. The synergistic removal efficiency of mercury by the air pollution control devices (APCDs) installed in the studied power plants is 66.69-97.56%. The Hg mass balance for the tested seven coal-fired power plants varied from 72.87% to 109.67% during the sampling time. After flue gas flowing through APCDs, most of the mercury in coal was enriched in fly ash and gypsum, with only a small portion released into the atmosphere with the flue gas. The maximum discharge source of Hg for power plants was fly ash and gypsum instead of Hg emitted with flue gas through the chimney into the atmosphere. With the continuous upgrading of APCDs, more and more mercury will be enriched in fly ash and gypsum. Extra attention should be paid to the re-release of mercury from the reutilization of by-products from APCDs. Implications: Method 30B and the Ontario Hydro Method (OHM) were used to test the mercury concentration in the flue gas discharged from seven power plants in Guizhou Province, China. The concentrations of mercury in coal samples, bottom ash, fly ash, and gypsum were also measured. By comparison of the mercury content of different products, we found that the maximum discharge source of Hg for power plants was fly ash and gypsum, instead of Hg emitted with flue gas through the chimney into the atmosphere. With the continuous upgrading of APCDs, more and more mercury will be enriched in fly ash and gypsum. Extra attention should be paid to the re-release of mercury from the reutilization of by-products from APCDs.


Asunto(s)
Contaminantes Atmosféricos , Monitoreo del Ambiente , Mercurio/análisis , Centrales Eléctricas/normas , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Atmósfera/análisis , Sulfato de Calcio/análisis , China/epidemiología , Ceniza del Carbón/análisis , Ceniza del Carbón/química , Exposición a Riesgos Ambientales/prevención & control , Monitoreo del Ambiente/instrumentación , Monitoreo del Ambiente/métodos , Monitoreo del Ambiente/normas , Predicción , Humanos
10.
ScientificWorldJournal ; 2014: 581724, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24737981

RESUMEN

Secondary atmospheric pollutions may result from wet flue gas desulfurization (WFGD) systems caused by the reduction of Hg(2+) to Hg(0) and lead to a damping of the cobenefit mercury removal efficiency by WFGD systems. The experiment on Hg(0) reemission from limestone-gypsum WFGD slurry was carried out by changing the operating conditions such as the pH, temperature, Cl(-) concentrations, and oxygen concentrations. The partitioning behavior of mercury in the solid and liquid byproducts was also discussed. The experimental results indicated that the Hg(0) reemission rate from WFGD slurry increased as the operational temperatures and pH values increased. The Hg(0) reemission rates decreased as the O2 concentration of flue gas and Cl(-) concentration of WFGD slurry increased. The concentrations of O2 in flue gas have an evident effect on the mercury retention in the solid byproducts. The temperature and Cl(-) concentration have a slight effect on the mercury partitioning in the byproducts. No evident relation was found between mercury retention in the solid byproducts and the pH. The present findings could be valuable for industrial application of characterizing and optimizing mercury control in wet FGD systems.


Asunto(s)
Carbonato de Calcio/química , Mercurio/química , Contaminación del Aire/prevención & control , Concentración de Iones de Hidrógeno , Temperatura
11.
ScientificWorldJournal ; 2014: 696429, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24672356

RESUMEN

With the government's emphasis on environmental issues of power transmission and transformation project, noise pollution has become a prominent problem now. The noise from the working transformer, reactor, and other electrical equipment in the substation will bring negative effect to the ambient environment. This paper focuses on using acoustic software for the simulation and calculation method to control substation noise. According to the characteristics of the substation noise and the techniques of noise reduction, a substation's acoustic field model was established with the SoundPLAN software to predict the scope of substation noise. On this basis, 4 reasonable noise control schemes were advanced to provide some helpful references for noise control during the new substation's design and construction process. And the feasibility and application effect of these control schemes can be verified by using the method of simulation modeling. The simulation results show that the substation always has the problem of excessive noise at boundary under the conventional measures. The excess noise can be efficiently reduced by taking the corresponding noise reduction methods.


Asunto(s)
Modelos Teóricos , Ruido
12.
Immunol Lett ; 105(1): 16-25, 2006 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-16388858

RESUMEN

Dendritic cell (DC) vaccine is a promising immunotherapy for malignancies, but its clinical efficacy has been questioned. Here we examined the mechanisms of treatment failure with DC vaccine in a murine colon cancer model. DC vaccination of naive mice prevents tumor implantation, but it is ineffective in tumor-bearing hosts despite the induction of tumor-specific CTL activity. Analyses of tumor-specific T helper cell type 1 (Th1)/T helper cell type 2 (Th2) responses showed that DC vaccine induced a mixed Th1/Th2 response in naive mice. Interestingly, CD4+ T cells from tumor-bearing mice showed a Th1-predominant response before DC vaccination but Th2 after DC vaccination. Furthermore, interleukin-10 production was higher in CD4+ T cells from vaccinated tumor-bearing mice than in CD4+ T cells from unvaccinated tumor-bearing mice. CD4+ T cells from mice treated with lipopolysaccharide (LPS)-matured DC fusion vaccine had lower production of interleukin-10 than CD4+ T cells from mice treated with non-LPS-treated DC vaccine. However, similar to the non-LPS-treated DC vaccine, the LPS-matured DC vaccine failed to suppress tumor growth and induced a Th2 predominant tumor-specific response in tumor-bearing mice. These results suggest that the presence of tumor in the host induces an aberrant CD4+ T cell response to DC vaccine, which may contribute to the failure of the vaccine to eradicate established tumors.


Asunto(s)
Vacunas contra el Cáncer/farmacología , Neoplasias del Colon/inmunología , Neoplasias del Colon/terapia , Células Dendríticas/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Antígenos de Neoplasias , Línea Celular Tumoral , Neoplasias del Colon/patología , Neoplasias del Colon/prevención & control , Células Dendríticas/efectos de los fármacos , Femenino , Técnicas In Vitro , Interleucina-10/biosíntesis , Interleucina-2/biosíntesis , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos BALB C , Modelos Inmunológicos , Linfocitos T Citotóxicos/inmunología , Células TH1/inmunología , Células Th2/inmunología
13.
Immunol Lett ; 101(2): 154-9, 2005 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-15993950

RESUMEN

Dendritic cell (DC)-based tumor vaccine is a promising therapy for malignancies. Recent studies showed greater potency with DC/tumor fusion vaccines against acute myeloid leukemia and melanoma compared with lysate-pulsed DC vaccines. We compared these two vaccine strategies against murine colon cancer and investigated whether DC/tumor fusion cells continue to produce tumor antigens following fusion as a possible explanation for their increased potency. Using a mouse colon cancer model, CT26, we first showed that the DC/CT26 fusion vaccine is more effective in preventing tumor implantation than CT26 lysate-pulsed DC vaccine. Next, CT26 made to constitutively produce bioactive TGF-beta, a surrogate of tumor-derived products, was fused to DCs and found to produce bioactive TGF-beta 72 h after fusion. Our results suggest the DC/tumor fusion vaccine is more potent against colon cancer than the lysate-pulsed DC vaccine. These fusion cells have the distinct advantage of prolonged interaction with tumor antigens in vivo.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Extractos Celulares/inmunología , Fusión Celular , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Células Dendríticas/citología , Células Dendríticas/inmunología , Animales , Antígenos de Neoplasias/metabolismo , Biomarcadores , Diferenciación Celular , Células Cultivadas , Neoplasias del Colon/metabolismo , Neoplasias del Colon/terapia , Femenino , Regulación de la Expresión Génica , Inmunoterapia , Ratones , Ratones Endogámicos BALB C , Tasa de Supervivencia , Factor de Crecimiento Transformador beta/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
14.
J Biol Chem ; 279(24): 25876-82, 2004 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-15075345

RESUMEN

Mutations in the leucine-rich repeat (LRR) domain of Nod2 have been implicated in the pathogenesis of Crohn's disease, yet the function of Nod2 and regulation of the Nod2 pathway remain unclear. In this study, we determined that mitogen-activated protein kinase kinase transforming growth factor (TGF)-beta-activated kinase 1 (TAK1) interacts with Nod2 and is required for Nod2-mediated NF-kappaB activation. The dominant negative form of TAK1 abolished muramyl dipeptide-induced NF-kappaB activation in Nod2-expressing cells. Nod2, acting in a reciprocal manner, inhibited TAK1-induced NF-kappaB activation in RICK-deficient embryonic fibroblasts. Nod2 appears to interact with TAK1 through its LRR region to exert its inhibitory effect on TAK1-induced NF-kappaB activation. Further, wild-type LRR more effectively suppressed NF-kappaB activation induced by TAK1 than LRR with a 3020insC mutation. Considered together, these findings demonstrate a critical role for TAK1 in Nod2-mediated innate immune responses and reveal a novel function for Nod2 in the regulation of the TAK1 signaling pathway.


Asunto(s)
Proteínas Portadoras/fisiología , Péptidos y Proteínas de Señalización Intracelular , Quinasas Quinasa Quinasa PAM/fisiología , Transducción de Señal , Animales , Proteínas Portadoras/química , Proteínas Portadoras/genética , Células Cultivadas , Enfermedad de Crohn/etiología , Humanos , Mutación , FN-kappa B/metabolismo , Proteína Adaptadora de Señalización NOD2 , Proteínas Quinasas/fisiología , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor
15.
Front Biosci ; 9: 448-56, 2004 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-14766381

RESUMEN

The role of Fas ligand (FasL) in tumor immune privilege is controversial. In this study, 22 human tumor cell lines reported to be FasL+ were reevaluated by Western blot analysis, ELISA, and a functional assay. None of the cells lines expressed FasL. To assess whether human tumors express FasL in vivo, susceptibility to FasL-mediated killing was evaluated. About 75% of the 22 tumors tested were sensitive to FasL-mediated apoptosis, suggesting, therefore, that only about 25% could possibly express FasL. To investigate whether "FasL+" human tumor cells could suppress the proinflammatory effects of FasL in vivo, FasL transfectants were generated from two prototype "FasL+" tumor cell lines. The transfectants expressing FasL were rejected by SCID mice. In contrast, all the mice inoculated with parental tumor cells developed large tumors. These results suggested that human tumor cells that express FasL and resist both FasL-mediated apoptosis and inflammation are rare or nonexistant. We concluded that FasL expression is not a main mechanism that tumors use to counteract antitumor immunity.


Asunto(s)
Glicoproteínas de Membrana/inmunología , Neoplasias/inmunología , Receptor fas/inmunología , Animales , Especificidad de Anticuerpos , Muerte Celular , Relación Dosis-Respuesta Inmunológica , Proteína Ligando Fas , Femenino , Humanos , Inmunidad , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Desnudos , Ratones SCID , Células Tumorales Cultivadas
16.
J Immunol ; 170(7): 3806-11, 2003 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-12646647

RESUMEN

Dendritic cell (DC)-based antitumor vaccine is a novel cancer immunotherapy that is promising for reducing cancer-related mortality. However, results from early clinical trials were suboptimal. A possible explanation is that many tumors secrete immunosuppressive factors such as TGF-beta, which may hamper host immune response to DC vaccine. In this study, we demonstrated that TGF-beta produced by tumors significantly reduced the potency of DC/tumor fusion vaccines. TGF-beta-secreting (CT26-TGF-beta) stable mouse colon cancer cell lines were generated using a retroviral vector expressing TGF-beta. A non-TGF-beta-secreting (CT26-neo) cell line was generated using an empty retroviral vector. The efficacies of DC/tumor fusion vaccines were assessed in vitro and in vivo. DC/CT26-TGF-beta fusion cells failed to induce a strong T cell proliferative response in vitro, mainly due to the effect of TGF-beta on T cell responsiveness rather than DC stimulatory capability. Animals vaccinated with DC/CT26-TGF-beta fusion vaccine had lower tumor-specific CTL activity and had significantly lower survival after tumor challenge as compared with animals immunized with DC/CT26-neo hybrids (45 vs 77%, p < 0.05). Ex vivo exposure of DCs to TGF-beta did not appear to lessen the efficacy of DC vaccine. These data suggest that tumor-derived TGF-beta reduces the efficacy of DC/tumor fusion vaccine via an in vivo mechanism. Neutralization of TGF-beta produced by the fusion cells may enhance the effectiveness of DC-based immunotherapy.


Asunto(s)
Vacunas contra el Cáncer/efectos adversos , Células Dendríticas/trasplante , Proteínas de Neoplasias/efectos adversos , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/prevención & control , Factores Supresores Inmunológicos/efectos adversos , Factor de Crecimiento Transformador beta/efectos adversos , Células Tumorales Cultivadas/trasplante , Animales , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Fraccionamiento Celular , Sistema Libre de Células/inmunología , Sistema Libre de Células/metabolismo , Técnicas de Cocultivo , Citotoxicidad Inmunológica/genética , Células Dendríticas/inmunología , Femenino , Inyecciones Intraperitoneales , Activación de Linfocitos/genética , Ratones , Ratones Endogámicos BALB C , Proteínas de Neoplasias/sangre , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/mortalidad , Factores Supresores Inmunológicos/sangre , Factores Supresores Inmunológicos/genética , Factores Supresores Inmunológicos/metabolismo , Subgrupos de Linfocitos T/inmunología , Linfocitos T Citotóxicos/inmunología , Factor de Crecimiento Transformador beta/administración & dosificación , Factor de Crecimiento Transformador beta/sangre , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1 , Células Tumorales Cultivadas/inmunología , Células Tumorales Cultivadas/metabolismo , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología
17.
Mamm Genome ; 13(2): 95-101, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11889557

RESUMEN

The human ATOH7 gene encodes a basic helix-loop-helix (bHLH) transcription factor that is highly similar to Drosophila Atonal within the conserved bHLH domain. The ATOH7 coding region is contained within a single exon. We mapped ATOH7 to Chromosome (Chr) 10q21.3-22.1, a region syntenic to the segment of mouse Chr 10 where Atoh7 (formerly Math5) is located. The evolutionary relationship between ATOH7 and other atonal homologs was investigated using parsimony analysis. A direct comparison of ATH5/7 and ATH1 protein subgroups to Atonal also revealed a nonrandom distribution of amino acid changes across the bHLH domain, which may be related to their separate visual and proprioceptive sensory functions. Among bHLH genes, ATOH7 is most closely related to Atoh7. This sequence conservation extends significantly beyond the coding region. We define blocks of strong homology in flanking human and mouse genomic DNA, which are likely to include cis regulatory elements. Because targeted deletion of Atoh7 causes optic nerve agenesis in mice, we propose ATOH7 as a candidate for human optic nerve aplasia and related clinical syndromes.


Asunto(s)
Mapeo Cromosómico , Proteínas de Unión al ADN/genética , Proteínas del Tejido Nervioso/genética , Células Ganglionares de la Retina/fisiología , Análisis de Secuencia de ADN , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Cromosomas Humanos Par 10 , Humanos , Ratones , Datos de Secuencia Molecular , Filogenia , Células Ganglionares de la Retina/citología , Sintenía
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