Mesothelioma Tumor Cells Modulate Dendritic Cell Lipid Content,Phenotype and Function

Dendritic cells (DCs) play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs) were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay), upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4⁺CD8α^- DCs, CD4^-CD8α^- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8⁺ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses.     

Comparison Study of Bone Defect Healing Effect of Raw and Processed Pyritum in Rats

To evaluate and compare the effect of raw and processed pyritum on tibial defect healing, 32 male Sprague Dawley rats were randomly divided into four groups. After tibial defect, animals were produced and grouped: sham and control group were orally administrated with distilled water (1 mL/100 g), while treatment groups were given aqueous extracts of raw and processed pyritum (1.5 g/kg) for successive 42 days. Radiographic examination showed that bone defect healing effect of the treatment groups was obviously superior compared to that of the control group. Bone mineral density of whole tibia was increased significantly after treating with pyritum. Inductively coupled plasma-optical emission spectrometry showed that the contents of Ca, P, and Mg in callus significantly increased in the treatment groups comparing with the control. Moreover, serological analysis showed that the concentration of serum phosphorus of the treatment groups significantly increased compared with that of the control group. By in vitro study, we have evaluated the effects of drug-containing serum of raw and processed pyritum on osteoblasts. It was manifested that both the drug-containing sera of raw and processed pyritum significantly increased the mRNA levels of alkaline phosphatase and collagen type I. Protein levels of phosphorylated Smad2/3 also increased. The mRNA levels of osteocalcin and transforming growth factor β (TGF-β) type I and II receptors, as well as the protein levels of TGF-β1 in the processed groups, were higher than those in the control. In summary, both raw and processed pyritum-containing sera exhibited positive effects on osteoblasts, which maybe via the TGF-β1/Smad signaling pathway. Notably, the tibia defect healing effect of pyritum was significantly enhanced after processing.     

A simple and precise aberrant translocation of the rat c-myc gene into the epsilon-heavy chain switch region of the IgE-producing immunocytoma, IR162

We report a simple type of reciprocal chromosomal translocation in the LOU rat IgE-secreting immunocytoma cell line, IR162, involving the c-myc protooncogene and the switch region of the epsilon immunoglobulin heavy chain, c-myc/S epsilon. By cloning and sequencing the translocation-associated and the homologous normal c-myc and S epsilon DNAs, we have identified the position of the translocational junction in both the c-myc 5'-flanking region and the repetitive elements of the S epsilon region. The translocational recombination was precise, and no insertion or N-addition was found in the junctional region, leaving all the c-myc exons, together with two promoter sites, intact. RNase mapping confirmed that the same promoters were utilized in IR162 and normal LOU spleen cells. No point mutation was found in the 5'-flanking region and the 3'-portion of exon 1 of the translocated c-myc gene. However, the putative silencer region was lost with the translocation. It was also noticed that a strikingly AT-rich sequence associated with S epsilon region had translocated to the 5'-flanking region of c-myc gene. We discuss the possibility that a change of DNA topology, perhaps either due to the juxtaposition of an AT-rich sequence of the S epsilon region, or to the loss of the putative silencer element, may contribute to c-myc gene deregulation in IR162.     

Responses of Crop Water Use Efficiency to Climate Change and Agronomic Measures in the Semiarid Area of Northern China

It has long been concerned how crop water use efficiency (WUE) responds to climate change. Most of existing researches have emphasized the impact of single climate factor but have paid less attention to the effect of developed agronomic measures on crop WUE. Based on the long-term field observations/experiments data, we investigated the changing responses of crop WUE to climate variables (temperature and precipitation) and agronomic practices (fertilization and cropping patterns) in the semi-arid area of northern China (SAC) during two periods, 1983–1999 and 2000–2010 (drier and warmer). Our results suggest that crop WUE was an intrinsical system sensitive to climate change and agronomic measures. Crops tend to reach the maximum WUE (WUEmax) in warm-dry environment while reach the stable minimum WUE (WUEmin) in warm-wet environment, with a difference between WUEmax and WUEmin ranging from 29.0%-55.5%. Changes in temperature and precipitation in the past three decades jointly enhanced crop WUE by 8.1%-30.6%. Elevated fertilizer and rotation cropping would increase crop WUE by 5.6–11.0% and 19.5–92.9%, respectively. These results indicate crop has the resilience by adjusting WUE, which is not only able to respond to subsequent periods of favorable water balance but also to tolerate the drought stress, and reasonable agronomic practices could enhance this resilience. However, this capacity would break down under impact of climate changes and unconscionable agronomic practices (e.g. excessive N/P/K fertilizer or traditional continuous cropping). Based on the findings in this study, a conceptual crop WUE model is constructed to indicate the threshold of crop resilience, which could help the farmer develop appropriate strategies in adapting the adverse impacts of climate warming.