An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Citation: Shi, Z. Z., Chapes, S. K., Ben-Arieh, D., & Wu, C. H. (2016). An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data. Plos One, 11(8), 39. doi:10.1371/journal.pone.0161131We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-a ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies

Effects of host plant genotype and seedbank density on Striga reproduction

Prevention of seed input to the seedbank of Striga hermonthica-infested fields is an important objective of Striga management. In three consecutive years of field experimentation in Mali, Striga reproduction was studied for 10 sorghum genotypes at infestation levels ranging from 30 000 to 200 000 seeds m−2. Host resistance was identified as an important determinant of Striga reproduction, with the most resistant genotypes (N13, IS9830 and SRN39) reducing Striga reproduction by 70–93% compared with the most susceptible genotype (CK60-B). Seedbank density had a significant effect on Striga seed production. Higher seedbank density resulted in more Striga plants, which led to increased intra-specific competition and consequently a reduced level of reproduction per plant. For the most susceptible sorghum genotypes, density dependence also occurred in the earlier belowground stages. Striga reproduction continued beyond harvest. At the high infestation level just 8% of the total reproduction was realised after harvest, whereas at the low infestation level 39% was attained after harvest. Even though host-plant genotype plays a significant role in Striga reproduction, calculations indicated that only at very low infestation levels the use of the most resistant genotype was able to lower the Striga seedbank

Effect of methanol extract of Dicranopteris linearis against carbon tetrachloride- induced acute liver injury in rats

Background: Dicranopteris linearis (family Gleicheniaceae) has been reported to possess anti-inflammatory and antioxidant activities but no attempt has been made to study its hepatoprotective potential. The aim of the present study was to determine the hepatoprotective effect of methanol extracts of D. linearis (MEDL) against carbon tetrachloride (CCl4)-induced acute liver injury in rats. Methods: 6 groups (n = 6) of rats received oral test solutions: 10% dimethyl sulfoxide (DMSO), 200 mg/kg silymarin, or MEDL (50, 250, and 500 mg/kg), once daily for 7 consecutive days, followed by hepatotoxicity induction with CCl4. Blood and liver were collected for biochemical and microscopic analysis. The extract was also subjected to antioxidant studies (e.g. 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging assays, oxygen radical absorbance capacity (ORAC) test and total phenolic content (TPC) determination), phytochemical screening and HPLC analysis. Results: Pretreatment with MEDL and silymarin significantly (P < 0.05) reduced the serum levels of AST, ALT and ALP, which were increased significantly (P < 0.05) in DMSO-pretreated group following treatment with CCl4. Histological analysis of liver tissues in groups pretreated with MEDL and silymarin showed mild necrosis and inflammation of the hepatocytes compared to the DMSO-pretreated group (negative control group). The MEDL showed higher DPPH- and superoxide anion-radical scavenging activity as well as high TPC and ORAC values indicating high antioxidant activity. Conclusions: MEDL exerts hepatoprotective activity that could be partly contributed by its antioxidant activity and high phenolic content, and hence demands further investigation