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.     

Development and evaluation of Trichoderma asperellum preparation for control of sheath blight of rice (Oryza sativa L.)

Sheath blight, which is caused by Rhizoctonia solani, is a disease that majorly impacts rice production. A biocontrol agent used for control rice sheath blight must be sprayed on the stem at specific times during rice growth, a process that is labour-intensive and renders the antagonist vulnerable to environmental factors. In this study, Trichoderma asperellum T12 was used to produce preparation by solid-state fermentation using a surface-response method. Rice hull was selected as a carrier based on its ability to sustain the T12 floating in the water and protect T12 from ultraviolet irradiation. The production of a T12-based preparation required 32% wheat bran, 7% inoculum, 2.3 g kg^?1 (NH₄)₂SO₄ and 65% water content, with fermentation at 27.5°C for 30 days and agitation every six days. The preparation demonstrated 90% biocontrol efficacy and significantly (P > 0.05) increased the seed-set rate and 1000-grain weight as compared with the pathogen treatment. The population of Trichoderma on the surface of rice leaf sheath in the treatment applied with T12 preparation increased from 232 cfu (colony forming units) g^?1 fw (fresh weight) to 436 cfu g^?1 fw during rice growth stage, which was significantly (P > 0.05) higher than pathogen treatment. The population of R. solani on the leaf sheath increased from 41 cfu g^?1 fw to 271 cfu g^?1 fw in the pathogen treatment, while remained stable (P > 0.05) at level of 10–23 cfu g^?1 fw in T12 preparation applied treatment. Biocontrol of sheath blight by the addition of the preparation to the soil is effective and decreases the costs of agro-industrial waste disposal.     

Synthesis and evaluation of novel substituted 5-hydroxycoumarin and pyranocoumarin derivatives exhibiting significant antiproliferative activity against breast cancer cell lines

A library of novel 5-hydroxycoumarin and pyranocoumarin derivatives was constructed via silica sulfuric acid-catalyzed pechmann reaction and Pd(0)-catalyzed suzuki coupling in tandem, and their antiproliferative activities against breast cancer cells MCF-7 and MDA-MB-231 were evaluated. The results showed that compounds such as 6b, 6d, 6h, and 6k possess significant antiproliferative activity against MCF-7 cell line with the IC₅₀ values of 7.2, 5.3, 3.3, and 6.5 μM, respectively.