Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily with diverse functions such as the transport of fatty acids and the induction of apoptosis. Previous reports indicated that expression of Lcn2 is induced under harmful conditions. However, the mechanisms of the induction of Lcn2 expression remain to be elucidated. In this report, we intended to identify the factor or factors that induce Lcn2 expression. Up-regulation of Lcn2 expression after X-ray exposure was detected in the heart, the kidney and especially in the liver. Primary culture of liver component cells revealed that this up-regulation in the liver was induced in hepatocytes. Up-regulation of Lcn2 expression was also detected in HepG2 cells after the administration of X-rays or H(2)O(2). Interestingly, up-regulation of Lcn2 expression after H(2)O(2) treatment was canceled by the addition of the anti-oxidants, dimethylsulfoxide or cysteamine. These results strongly suggest that Lcn2 expression is induced by reactive oxygen species. Therefore, Lcn2 could be a useful biomarker to identify oxidative stress both in vitro and in vivo.

The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that the forced expression of the C-X-C chemokine receptor type 6 (CXCR6, whose ligand is highly expressed by human and murine pancreatic cancer cells and by tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell-adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained antitumoral activity and prolonged animal survival only when co-expressing CXCR6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.

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Despite their popularity, little research has been performed on lightly cooked and raw diet formats for pets. Therefore, the objective of this study was to determine the apparent total tract macronutrient digestibility (ATTD); fecal characteristics, metabolites, and microbiota; serum chemistry metabolites; urinalysis; and voluntary physical activity levels of adult dogs fed commercial diets differing in processing type. The diets included: 1) Extruded Dry Kibble (EXT) diet; 2) High-Moisture Roasted Refrigerated (RR) diet; 3) High-Moisture Grain-Free Roasted Refrigerated (GFRR) diet; and 4) Raw (RAW) diet. Eight dogs (mean age = 3.6; mean BW = 13.0 kg) were used in a replicated 4x4 Latin square design. Each period consisted of 28 d, with a 14-d adaptation phase followed by a 7-d phase for measuring voluntary physical activity, 1-d adaptation phase to metabolic cages, 5-d phase for fecal and urine collection, and 1 d for blood collection. Except for microbiota, all data were analyzed statistically by mixed models using SAS. Microbiota data were analyzed using Quantitative Insights Into Microbial Ecology (QIIME) and Statistical Analyses of Metagenomic Profiles (STAMP) software. Many differences in digestibility were observed, including greater (P<0.05) ATTD of crude protein and fat in dogs fed GFRR and RR than dogs fed EXT. Dogs fed RAW had the lowest fecal pH and dry matter %, but fecal scores were not affected. Dogs fed RR had higher (P<0.05) fecal indole and total phenol and indole concentrations than dogs fed the other diets. Dogs fed RAW had a higher (P<0.05) fecal ammonia concentration than dogs fed the other diets. Fecal microbial diversity was altered by diet, with dogs fed GFRR and RAW having reduced species richness than dogs fed EXT. Dogs fed RR, GFRR, or RAW had lower (P<0.05) Actinobacteria and higher (P<0.05) Fusobacteria than dogs fed EXT. Dogs fed RAW or GFRR had higher (P<0.05) Proteobacteria than dogs fed EXT or RR. Dogs fed RAW had higher (P<0.05) Bacteroidetes and lower (P<0.05) Firmicutes than dogs fed EXT. Serum triglycerides were within reference ranges, but greater (P<0.05) in dogs fed EXT than dogs fed GFRR and RAW. All diets were well tolerated and dogs remained healthy throughout the study. In conclusion, the lightly cooked and raw diets tested were highly palatable, highly digestible, reduced blood triglycerides, maintained fecal quality and serum chemistry, and modified the fecal microbial community of healthy adult dogs.