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The orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC) are known to participate in risk-based decision-making. However, whether neuronal activities of these two brain regions play similar or differential roles during different stages of risk-based decision-making process remains unknown. Here we conducted multi-channel in vivo recordings in the OFC and mPFC simultaneously when rats were performing a gambling task. Rats were trained to update strategy as the task was shifted in two stages. Behavioral testing suggests that rats exhibited different risk preferences and response latencies to food rewards during stage-1 and stage-2. Indeed, the firing patterns and numbers of non-specific neurons and nosepoking-predicting neurons were similar in OFC and mPFC. However, there were no reward-expecting neurons and significantly more reward-excitatory neurons (fired as rats received rewards) in the mPFC. Further analyses suggested that nosepoking-predicting neurons may encode the overall value of reward and strategy, whereas reward-expecting neurons show more intensive firing to a big food reward in the OFC. Nosepoking-predicting neurons in mPFC showed no correlation with decision-making strategy updating, whereas the response of reward-excitatory neurons in mPFC, which were barely observed in OFC, were inhibited during nosepoking, but were enhanced in the post-nosepoking period. These findings indicate that neurons in the OFC and mPFC exhibit distinct responses in decision-making process during reward consumption and strategy updating. Specifically, OFC encodes the overall value of a choice and is thus important for learning and strategy updating, whereas mPFC plays a key role in monitoring and execution of a strategy.

Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis caused by schistosomiasis. Chemokines were widely expressed and involved in cellular activation, proliferation and migration in inflammatory and infectious diseases. However, little is known about the expressions of chemokines on HSCs in the schistosoma infection. In addition, the roles of chemokines in pathogenesis of liver fibrosis are not totally clear. In our study, we used microarray to analyze the temporal gene expressions of primary HSCs isolated from mice with both acute and chronic schistosomiasis. Our microarray data showed that most of the chemokines expressed on HSCs were upregulated at 3 weeks post-infection (p.i) when the egg granulomatous response was not obviously evoked in the liver. However, some of them like CXCL9, CXCL10 and CXCL11 were subsequently decreased at 6 weeks p.i when the granulomatous response reached the peak. In the chronic stage, most of the differentially expressed chemokines maintained persistent high-abundances. Furthermore, several chemokines including CCR2, CCR5, CCR7, CXCR3, CXCR4, CCL2, CCL5, CCL21, CXCL9 and CXCL10 were expressed by HCSs and the abundances of them were changed following the praziquantel treatment in the chronic stage, indicating that chemokines were possibly necessary for the persistence of the chronic stage. In vitro experiments, hepatic non-parenchymal cells, primary HSCs and human HSCs line LX-2 were stimulated by chemokines. The results showed that CXCL9 and CXCL10, but not CXCL11 or CXCL4, significantly inhibited the gene expressions of Col1α1, Col3α1 and α-SMA, indicating the potential anti-fibrosis effect of CXCL9 and CXCL10 in schistosomiasis. More interestingly, soluble egg antigen (SEA) of Schistosoma japonicum was able to inhibit transcriptional expressions of some chemokines by LX-2 cells, suggesting that SEA was capable of regulating the expression pattern of chemokine family and modulating the hepatic immune microenvironment in schistosomiasis.

Background Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required. Methods and findings The antifibrotic effects of praziquantel were assessed in the murine models of schistosomiasis japonica. Murine fibrosis models were established by cutaneous infection with 14 ± 2 Schistosoma japonicum cercariae. Then, the mice of both chronic (8 weeks post-infection) and advanced (15 weeks post-infection) schistosomiasis were treated by gavage of praziquantel (250 mg/kg, once daily for 3 days) to eliminate worms, and followed by praziquantel anti-fibrosis treatment (300 mg/kg, twice daily for 30 days). The fibrosis-related parameters assessed were areas of collagen deposition, content of hydroxyproline and mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9, TIMP1, IL-4, IL-10, IL-13 and IFN-γ of liver. Spleen weight index, alanine aminotransferase activity and liver portal venous pressure were also measured. The results showed that anti-fibrosis treatment improved liver fibrosis, splenomegaly, hepatic function, as well as liver portal hypertension. In order to confirm the anti-fibrotic properties of praziquantel, we established a CCL(4)-induced model and revealed that CCL(4)-induced liver fibrosis was inhibited by PZQ treatment for 30 days. Furthermore, we analyzed the effects of praziquantel on mouse primary hepatic stellate cells (HSCs). It is indicated that mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9 and TIMP1 of HSCs were all inhibited after praziquantel anti-parasite treatments. Conclusions The significant amelioration of hepatic fibrosis by praziquantel treatment validates it as a promising drug of anti-fibrosis and offers potential of a new chemotherapy for hepatic fibrosis resulting from schistosomiasis.

To study changes of inflammation-associated cytokine expressions during early phase of endotoxic shock in macaque.Experiments were performed in Macaque mulatta treated with LPS 2.8 mg/kg in shock model group or with normal saline in control group. Blood samples were collected before, or 60 min, or 120 min after LPS injection, respectively. Liver and spleen tissues were obtained at 120 min after LPS injection. The plasma levels of TNF-alpha, IL-1beta, IL-10 and IL-12P40 were determined by double-antibody sandwich ELISA with antibodies against human cytokines. The mRNA levels of TNF-alpha, IL-1beta, and IL-18 in peripheral blood mononuclear cells (PBMCs), liver and spleen were examined by real-time fluorescence semi-quantitative RT-PCR with the primers based on human genes.Mean systemic arterial pressure (MAP), systemic vascular resistance index (SVRI) and left ventricular work index (LVWI) of macaques were significant declined in shock model group on average 60 min after LPS injection. The plasma levels of TNF-alpha and IL-10 were significantly increased 60 min after LPS injection and then decreased. The plasma levels of IL-1beta and IL-12P40 were significantly increased at 120 min after LPS injection. The mRNA levels of TNF-alpha and IL-1beta were significantly increased 60 min after LPS stimulation in PBMCs and 120 min after LPS stimulation in livers. The mRNA level of IL-18 was significantly increased 120 min after LPS stimulation in PBMCs and livers. But in spleen, only TNF-alpha mRNA level in LPS group was significantly higher 120 min after LPS stimulation, compared with that in control group.An endotoxic shock model of Macaque mulatta was successfully established. Both antibodies for ELISA and PCR primers based on human cytokine assays were successfully applied to detect macaque cytokines. In the model, inflammatory cytokines, such as TNF-alpha, IL-1beta, IL-12 and IL-18 as well as anti-inflammation cytokine IL-10, were released at very early phase of endotoxic shock within 120 min after LPS injection. PBMCs and liver cells might be the important sources of these cytokines.