P38 activation is more important than ERK activation in lung injury induced by prolonged hyperbaric oxygen.

Prolonged exposure to hyperbaric oxygen can cause pulmonary and nerve system toxicity. Although hyperbaric oxygen treatment has been used for a broad spectrum of ailments, the mechanisms of prolonged hyperbaric oxygen-induced lung injury are not fully understood. The purpose of the present work was to investigate the roles of ERK, p38, and caspase-3 in rat lung tissue exposed to hyperbaric oxygen at 2.3 atmospheres absolute (atm abs) for two, six and 10 hours. The results showed that the ERK and p38 were phosphorylated at two hours and reached a peak at six hours into exposure to hyperbaric oxygen. While the phosphorylation level of ERK decreased, p38 remained at a high level of activation at 10 hours. The activation of ERK and p38 was down-regulated when rats were exposed to normoxic hyperbaric nitrogen for 10 hours. However, caspase-3 was activated at six hours and 10 hours into exposure to hyperbaric oxygen. These results demonstrated different changes of activation of ERK and p38 during lung injury induced by prolonged exposure to hyperbaric oxygen. The time course changes of activated caspase-3 were similar to the process of p38 activation upon exposure to hyperbaric oxygen. In this way, activation of p38, not ERK, seems to be a mechanism associated with prolonged hyperbaric oxygen-induced lung injury.

[Establishment of a SCID mouse model for synergistic anti-tumor effect of human IL-12 and B7-1].

Human IL-12(hIL-12) has weak effect on mouse immunity cells, so the practical animal model is not available for the study of hIL-12 anti-tumor activity. In this work, the improved Winn assay was applied to evaluate the synergistic anti-tumor effects of hIL-12 and human costimulatory molecule B7-1(hB7-1) on human tumor in HuPBL-SCID mouse model. Three gene transferring solutions hIL-12, hB7-1 and their mixture(1:1) were prepared using the nonliposome transgene reagent and the expressing vectors, and hIL-12, hB7-1 or their mixture were transferred into tumor cell A375 respectively. Then A375 were co-injected into SCID mice with HuPBL, and rhIL-2 were injected i.p. as an anti-tumor agitator. On the other hand, LoVo and SPC tumor cells were also used to test the inhibitory effect of the mixture of hIL-12 and hB7-1. The anti-tumor effect of transferred genes was estimated by detecting tumor inhibition rate. Furthermore, the histochemical change of A375 implanting tumor tissue was also observed. Results showed that, to A375, the tumor inhibition rate of hIL-12, hB7-1, or their mixture were 74.06%, 66.98%, and 93.40%, respectively (P<0.01); and the mixture showed a good synergistic effect according to the Webb s fraction multiplication law. The tumor inhibition rate of the mixture in LoVo and SPC implanted mice were 98.37% and 97.39% respectively, also showing a good synergistic effect. Histochemical study in A375 implanted mice showed that in gene transfected mice, tumor cells were greatly inhibited and fully intruded by HuPBL cells; while in control group, tumor cells grew very well and HuPBL showed a conglomeration. At last, the human IgG and T cells in PBL of HuPBL-SCID mice were higher than non-HuPBL-SCID mice implanted A375; which showed that HuPBL-SCID mice could be applied for the evaluation of the anti-tumor effect of human IL-12 and B7-1. All data indicated that the combination of hIL-12 and hB7-1 gene might be a promising approach for in vivo cancer therapy.