Resumen Antecedentes: La enfermedad de injerto contra huésped (EICH) es una complicación importante después del trasplante alogénico de células madre hematopoyéticas. Objetivos: Para dilucidar el papel de TLR4, el principal receptor de LPS bacteriano, en el desarrollo de GVHD, construimos un modelo de GVHD en ratones knockout para TLR4 (TLR4-/-) y monitoreamos el quimerismo celular. Métodos: En este estudio, usamos PCR para identificar si se establecieron ratones knockout para TLR4 (TLR4-/-). Antes del trasplante, pretratamos a los ratones con irradiación para obtener la dosis de irradiación adecuada. Se aplicó citometría de flujo para medir el estado de quimerismo, las distribuciones de APC y células T en ratones receptores TLR4+/+ y TLR4-/-. Resultados: El estado general de los receptores de TLR4-/- fue mejor que el de los receptores de TLR4+/+, y los ratones receptores de TLR4-/- mostraron manifestaciones de GVHD menos graves que los ratones receptores de TLR4+/+. La mayoría de las APC y las células T en el bazo del ratón huésped se derivaron de las células del donante, y las células T CD4+, incluidas las células T de memoria, se encontraban en su mayoría en los ratones huéspedes. Conclusión: En general, nuestros datos muestran que la eliminación de TLR4 atenuó el desarrollo de GVHD, lo que sugiere que TLR4 podría usarse como un nuevo objetivo y paradigma terapéutico en las terapias de GVHD.

Abstract Background: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Objective: To elucidate the role of Toll-like receptor 4 (TLR4), the major receptor for bacterial lipopolysaccharide, in the development of GVHD, we constructed a GVHD model in TLR4 knockout (TLR4-/-) mice and monitored the cell chimerism. Methods: In this study, we used polymerase chain reaction to identify whether TLR4 knockout (TLR4-/-) mice were established. Before transplantation, we pretreated mice with irradiation so as to obtain an appropriate irradiation dose. Flow cytometry was applied to measure the chimerism status, the distributions of antigen-presenting cells (APCs), and T-cells in TLR4+/+ and TLR4-/- recipient mice. Results: The general condition of TLR4-/- recipients was better than that of TLR4+/+ recipients, and the TLR4-/- recipient mice showed less severe GVHD manifestations than the TLR4+/+ recipient mice. Most of the APCs and T-cells in the host mouse spleen were derived from donor cells, and CD4+ T-cells, including memory T-cells, were in the majority in host mice. Conclusion: In general, our data show that TLR4 deletion attenuated GVHD development, which suggests that TLR4 could be used as a novel target and therapeutic paradigm in GVHD therapies.

Abstract Purpose of this study the mechanism of curcumin inhibiting pyroptosis in infectious acute lung injury through NLRP3 inflammatory pathway. In this study, SPF SD male rats were randomly divided into blank control group, curcumin group, lipopolysaccharide (LPS) group, LPS + curcumin group, LPS + Nigerin treatment group, LPS + Nigerin + curcumin treatment group. Three in each group. Animal models were established according to the experimental design. Blood samples were collected after anesthesia, and the lung wet/dry weight ratio was calculated. TUNEL was used to detect pyroptosis of alveolar macrophages in left lower lobe, and Elisa was used to detect the expression levels of inflammatory factors IL-1β and IL-18 in left lung tissue. Western Blot was used to detect the expression of pyroptosis-related proteins such as NLRP3, Caspase1 and GSDMD in right lung alveolar lavage fluid. Compared with the blank control group, the lung wet weight and lung dry weight of the curcumin group were significantly increased (P < 0.01, P < 0.05). Compared with the LPS group, the lung wet weight and lung dry weight of the curcumin group There was a statistical difference in weight increase (P < 0.01). Compared with the blank control group, the apoptosis rate of lung tissue in the curcumin group, LPS group and LPS+ nigericin group was significantly increased (P < 0.01). Compared with the LPS + nigericin group, the lung tissue apoptosis rate in the LPS + curcumin + nigericin group was decreased, but there was no statistical difference (P > 0.05). LPS and LPS combined with Nigerian bacteriocin can cause pyroptosis in lung tissue. Curcumin can inhibit pyroptosis of lung tissue macrophages caused by LPS and LPS combined with Nigerian bacteriocin, and reduce inflammatory response.

Abstract Purpose: To investigate the therapeutic benefits of Hydroxysafflor yellow A (HSYA) on blood-brain barrier (BBB) vulnerability after traumatic brain injury (TBI) and identify its potential action of mechanisms on TBIinduced injuries. Methods: The rat TBI model was performed by using a controlled cortical impact device. The BBB permeability induced by TBI was measured through Evans Blue dye superflux and western blotting or polymerase chain reaction (PCR) for tight junctional proteins (TJPs). The post-TBI changes in oxidative stress markers, inflammatory response and neuron apoptosis in brain tissue were also tested. Results: Herein, the results showed that HSYA acutely attenuated BBB permeability via increasing the production of the TJPs, including occludin, claudin-1 and zonula occludens protein 24 h after TBI. Additionally, HSYA could suppress the secretion of proinflammatory factors, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α (IL-1β, IL-6, and TNF-α), and also concurrently down-regulate the expression of inflammation-related Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-kB) protein. These HSYA challenged changes were accompanied by the decreased TBI induced oxidative stress markers and inhibited the expression of apoptosis proteins Bax, caspase-3 and caspase-9. Conclusions: Taken together, all findings suggested that HSYA (30 mg/kg) are against TBI through improving the integrity in BBB, which are associated with the antioxidant, anti-inflammation and antiapoptosis via the probable mechanism of down-regulation of the TLR4/NF-kB pathway, and its in-detail protective mechanisms are under study.

The catalysts by incipient wetness impregnation method were prepared and characterized by XRD, BET, H2-TPD, NH3 -TPD and H2-TPR analysis, and the catalyst activity was detected by WFSM-3060 high-pressure reactor. Effective double metal catalysts were produced by using y-Al2O3 as carrier and Co and Ni as activity center, and more effectiveness by using Ce to modify. The results revealed that the 15Co5Ni-10Ce catalyst was the best in producing bio-fuels. The catalyst had good thermal stability, three kinds of adsorbed sites and three kinds of acidic sites. Compared with sintering, the catalyst deactivation was due to coke deposition. The results of FT - IR, SF-3, GC and GC-MS indicated that reaction temperature is the key factor and that oil velocity is a very important factor. The optimized condition was at reaction temperature of 450°C, reaction pressure of 3.0 MPa, oil velocity of 0.1 mL/min and the gas velocity of 35 mL/min, respectively. The alkanes and alkenes content of liquid products are 50.02% and 40.03% under the optimized condition. The main products are the hydrocarbon compounds under C18. The results of GC online and trace water determination showed that the main products of oxygen in the oil are CO and CO2, and that the minor product is H2O. The importance and the economical production of the Non-ester renewable diesel from vegetable oil are presented. From the results of FT-IR, SF-3 and GC-MS, the generating mechanism of Non- ester renewable diesel was deduced.

A spectrophotometric method for the simultaneous determination of norfloxacin, ofloxacin and lomefloxacin, is described. The spectrophotometric analysis is made possible with the aid of chemometric methods, such as classical least square (CLS), principal component regression (PCR), partial least square (PLS), and radial basis function-artificial neural network (RBF-ANN). Spectra were collected in the 190-400 nm range from a set of samples of three compounds in a Britton-Robinson buffer solution (pH=1.81). This approach overcomes the significant practical difficulties of severe spectral overlap. It was found that peak intensities are proportional to the concentration for each analyte. The obtained linear calibration concentration ranges are 0.6-13.8, 0.5-15.0, and 0.5-15.0 mg L-1 for norfloxacin, ofloxacin and lomefloxacin, respectively, and the LODs for the three analytes were found to be approximately 6-24x 10-2 mg L-1 . The proposed method was applied to a prediction set of synthetic mixtures of three analytes. The results were shown that the RBF-ANN model gave the best results (RPE T = 3.0%). This method was also applied for the determination of norfloxacin, ofloxacin and lomefloxacin in rabbit blood serum, and these compared well with those from the alternative analysis by HPLC.