A comprehensive analysis of initial thymus size and involution rate has not been quantitated for different genetic backgrounds of mice, thus genetic linkage analysis of thymic involution has not been possible. Here, we have used a mathematical method to analyze the age-related decline in thymocyte count in C57BL/6 and DBA/2 mice and have observed that thymic involution could be best fit with a negative exponential curve N(t) ¼ b 0 Â exp(Àb 1 t), where t represents the age (day). This regression model was applied to C57BL/6 Â DBA/2 (B Â D) recombinant inbred strains of mice to identify the genetic loci influencing agerelated thymic involution. There was a dramatic genetic effect of B and D alleles on thymocyte count at young age and the agerelated thymic involution rate. The strongest quantitative trait loci (QTL) influencing the rate of thymic involution were mapped to mouse chromosome (Chr) 9 (D9Mit20 at 62 cM) and Chr 10 (D10Mit61 at 32 cM). The strongest QTLs influencing the initial thymocyte count were mapped to ChrX (DXMit324 at 26.5 cM) and Chr 3 (D3Mit127 at 70.3 cM). The present study suggests that the initial thymus size and the rate of thymic involution may be influenced by a relatively small number of genetic loci.

The elevation of soluble Fas (sFas) in the sera of patients with liver disease suggests a role for sFas in the disease process; whether it is protective or not is controversial. To determine the effects of sFas on Fas-induced liver apoptosis, we manipulated mice to produce sFas by transfecting them in vivo with different amounts of an adenovirus that produces mouse sFas driven by the CMV promoter (AdsFas). Fasmediated apoptosis was induced by administration of antimouse Fas (Jo2; 10 m mg/mouse) one week later. The administration of AdsFas (10 3 , 10 7 , or 10 9 pfu/mouse), which was associated with only minimal side-effects, resulted in a significant reduction in the liver transaminase levels and mortality of the mice on challenge with Jo2, as compared to control mice treated with AdLacZ. However, the protective effect of AdsFas was not complete. The possibility that Jo2-induction of TNF-a a in the Kupffer cells of the liver contributes to the pathology was therefore tested. Although administration of soluble TNF receptor (sTNFRI) alone did not protect the mice from the lethal effects of Jo2, administration of sTNFRI (200 m mg/mouse) after infection with AdsFas (10 9 pfu/mouse) resulted in 100% survival of the mice on challenge with Jo2. To confirm that the production of TNF-a a by Kupffer cells produce the lethal effects of Jo2 that remained after treatment with AdsFas, these cells were selectively ablated by treatment of the mice with gadolinium chloride prior to challenge with Jo2. This treatment greatly reduced early mortality and hepatocellular damage as well as TNF-a a production 6 h after injection of Jo2. These results indicate that: (1) AdsFas prevents Jo2-induced apoptosis of hepatocytes; (2) In addition to mediating Fas-mediated apoptosis of hepatocytes, Jo2 can separately induce TNF-a a production by Kupffer cells resulting in early mortality, and (3) Optimal protection from Jo2-induced mortality can be achieved by protection of liver cells by pretreatment with both AdsFas and sTNFRI.

Introduction Hepatoma is the leading cause of death among liver diseases worldwide. Modern pharmacological studies suggest that some natural monomeric compounds have a significant effect on inhibiting tumor growth. However, poor stability and solubility, and side effects are the main factors limiting the clinical application of natural monomeric compounds. Methods In this paper, drug-co-loaded nanoself-assemblies were selected as a delivery system to improve the chemical stability and solubility of Tanshinone II A and Glycyrrhetinic acid, and to produce a synergetic anti-hepatoma effect. Results The study suggested that the drug co-loaded nanoself-assemblies showed high drug loading capacity, good physical and chemical stability, and controlled release. In vitro cell experiments verified that the drug-co-loaded nanoself-assemblies could increase the cellular uptake and cell inhibitory activity. In vivo studies verified that the drug co-loaded nanoself-assemblies could prolong the MRT 0-∞ , increase accumulation in tumor and liver tissues, and show strong synergistic anti-tumor effect and good bio-safety in H22 tumor-bearing mice. Conclusion This work indicates that natural monomeric compounds co-loaded nanoself-assemblies would be a potential strategy for the treatment of hepatoma.

Introduction Multiple studies in different countries show a trend of adolescents having insufficient sleep. Review of literature strongly suggests role of cytokines in sleep regulation. Different inflammatory markers like tumor necrosis factor (TNF)α, C-reactive protein (CRP) and interleukins (IL) are sleep regulatory substances. Most of the studies showing relation between cytokines and sleep are seen in adults. In our study, we were interested in finding the relationship between sleep quality and inflammatory markers in healthy adolescents. Methods Twenty eight female and male, African American and White, healthy adolescents aged 15–18 completed the study. Sleep quality was measured using the Pediatric Sleep Questionnaires (PSQ), including snoring, daytime sleepiness and hyperactive behavior. Blood sample was collected from each participant for measuring the inflammatory factors. Results Partial Pearson correlation analysis showed that global PSQ score and hyperactive behavior were significantly correlated with TNF α (r=0.37 for both). Snoring was significantly correlated with leptin, CRP and IL-6 in healthy adolescents. No other correlations were observed. Conclusion Consistent with findings in adults, we have observed an association between inflammatory markers and poor sleep in healthy adolescents. Our findings suggest the importance to improve sleep quality in adolescents for better health outcomes. Support None of the authors have any conflict of interest. This research was supported by awards, P30DK056336 and P30DK079626, from the National Institute of Diabetes And Digestive And Kidney Diseases to Nutrition Obesity Research Center and Diabetes Research Center, respectively, at the University of Alabama at Birmingham.