RESUMEN
UNLABELLED: BACKGROUND: Uncontrolled hapatic inflammatory response is regarded as the primary pathological mechanism of acute liver failure and impairs the regeneration of hepatocytes and stem cell grafts. Interleukin-1 plays a key role for activating immune and inflammatory response. Recently, siRNA has made quite a few progresses in treating inflammatory response. AIM: To assess the effect of IL-1? siRNA adenovirus on MSC and the therapeutic effect of MSC combined with IL-1? siRNA adenovirus in ALF. MATERIAL AND METHODS: We implanted MSC or/and IL-1? siRNA adenovirus via the tail vein, using CCl4-induced ALF in a mice model. Mice were sacrificed at different time points. Blood samples and liver tissues were collected. Hepatic injury, liver regeneration, cytokines (CXCL1, IL-1?, IL-10, IL-6, VEGF and HGF), animal survival and vital MSC were assessed after cell transplantation. RESULTS: MSC combined with IL-1? siRNA reduced the inflammatory levels and prevented liver failure. These animals administrated with MSC and IL-1? siRNA also exhibited improved liver regeneration and increased survival rates. Immunohistochemistry and fluorescence microscopy revealed the number of vital MSC in ALF + MSC + IL-1? siRNA group were significantly more than that in ALF + MSC group. CONCLUSION: IL-1? siRNA adenovirus could enhance MSC ability of tissue regeneration through increasing its survival rate. Accordingly, combination of IL-1? siRNA adenovirus and MSC had a synergistic effect on acute liver failure.
Asunto(s)
Interleucina-1beta/efectos de los fármacos , Fallo Hepático Agudo , Regeneración Hepática/efectos de los fármacos , Hígado/efectos de los fármacos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/efectos de los fármacos , ARN Interferente Pequeño/farmacología , Adenoviridae , Animales , Quimiocina CXCL1/efectos de los fármacos , Quimiocina CXCL1/inmunología , Factor de Crecimiento de Hepatocito/metabolismo , Inflamación , Interleucina-10/inmunología , Interleucina-6/inmunología , Hígado/inmunología , Hígado/metabolismo , Regeneración Hepática/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Tratamiento con ARN de Interferencia , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
With combined microfiltration (MF)/ultrafiltration (UF) and reverse osmosis (RO) process being widely used in municipal wastewater reclamation, RO concentrate with high level genotoxicity is becoming a potential risk to water environment. In this study, wastewater genotoxicity in a MF-RO process for municipal wastewater reclamation and also the effects of chemical agent injections were evaluated by SOS/umu genotoxicity test. The genotoxicity of RO concentrate ranged 500-559 µg 4-NQO (4-nitroquinoline-1-oxide)/L and 12-22 µg 4-NQO/mg DOC, was much higher than that of RO influent. Further research suggested that Kathon biocide was a key chemical agent associated with the genotoxicity increase. Kathon biocide used in RO system was highly genotoxic in vitro and Kathon biocide retained in RO system could contribute to a higher genotoxicity of RO concentrate. Hence, treatments for biocides before discharging are necessary. Chlorination of secondary effluent could significantly decrease the genotoxicity and increasing chlorine dosage could be an efficacious method to decrease the genotoxicity of RO concentrate. According to the result of the experiment, the dosage of chlorine in dual-membrane process could be set to about 2.5 mg Cl2/L. The effect of antiscalant (2-phosphomobutane-1,2,4-tricarboxylic acid) was also investigated; it turned out to have no effect on genotoxicity.