The intake of ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA) increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ12,14-PGJ3 (15d-PGJ3), a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ)-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s) for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation.

Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in the pancreatic cancer microenvironment. Here, we show that neoplastic pancreatic epithelium, as well as a subset of tissue-resident macrophages, expresses the prolactin-receptor (PRLR). High mobility group box 1-induced prolactin expression in the pancreas maintained FAK1 and STAT3 phosphorylation within the epithelium and stroma. Gain-of-function and loss-of-function experiments demonstrated the essential role of prolactin in promoting collagen deposition and fibrosis. Finally, the signaling cascade downstream of prolactin/ PRLR activated STAT3 rather than STAT5 in PDAC. These findings suggest that targeting prolactin together with IL6, a known major activator of STAT3, could represent a novel therapeutic strategy for treating pancreatic cancer.Significance: Prolactin is a key factor in the cross-talk between the stroma and neoplastic epithelium, functioning to promote fibrosis and PDAC progression.

The effect of heat treatment and dietary fiber from whole and dehulled black bean (Phaseolus vulgaris) seeds on digestibility of various starches by bovine, porcine and human pancreatic a-amylases was studied. Corn, rice, wheat and black bean starch digestibility increased after heating. The degree of hydrolysis of black bean starch ranged between 56 and 83% of the values obtained for cereal starches depending on the enzyme used. Enzyme activity was: human-> porcine > bovine regardless of the substrate employed. Dietary fiber decreased starch digestibility by porcine enzyme. This effect was more marked when whole grain fiber was used. Black bean and rice starch digestibility by human amylase was not affected by fiber, while corn and wheat starch hydrolysis was slightly inhibited. The use of the human enzyme is recomended for in uitro amylolysis assays. Attention is called on the difficulties of extrapolating results obtained with animal enzymes to humans. In vitro-Verdaulichkeit von Getreide-und Leguminosen-(Phaseolus vulgaris)-Starken durch Rinder-, Schweine-undMenschen-Pankreas-a-Amylasen. Der EinfluR der Rohfaser. Der EinfluR von Hitzebehandlung und Rohfaser aus ganzen und geschalten Schwarzbohnen-(Phaseolus vulgaris)-Samen auf die Verdaulichkeit verschiedener Starken durch Rinder-, Schweine-und Menschen-Pankreas-a-Amylasen wurde untersucht . Die Verdaulichkeit von Mais-, Reis-, Weizen-und Schwarzbohnenstarke war nach der Erhitzung erhoht. Der Hydrolysegrad der Schwarzbohnenstarke lag zwischen 56 und 83% der fur Getreidestarken in Abhangigkeit von dem verwendeten Enzym erhaltenen Werte. Die Enzymaktivitat war: Mensch > Schwein > Rind, unabhanig von dem eingesetzten Substrat. Dieser Effekt wurde deutlicher, wenn Ganzkornfaser verwendet wurde. Die Verdaulichkeit von Schwarzbohnen-und Reisstarke durch menschliche Amylase wurde durch Faser nicht beeintrachtigt, wahrend die Hydrolyse von Mais-und Weizenstarke gering inhibiert wurde. Die Verwendung von menschlichem Enzym wird fur die in vim-Amylolyse-Versuche empfohlen. Auf die Schwierigkeiten der Extrapolierung von mit tierischen Enzymen erhaltenen Ergebnissen auf menschliche Enzyme wird aufmerksam gemacht .

Mutations of the TRPS1 gene cause trichorhinophalangeal syndrome (TRPS), a skeletal dysplasia with dental abnormalities. TRPS dental phenotypes suggest that TRPS1 regulates multiple aspects of odontogenesis, including the tooth number and size. Previous studies delineating Trps1 expression throughout embryonic tooth development in mice detected strong Trps1 expression in dental mesenchyme, preodontoblasts, and dental follicles, suggesting that TRPS dental phenotypes result from abnormalities in early developmental processes. In this study, Trps1 +/− and Trps1 −/− mice were analyzed to determine consequences of Trps1 deficiency on odontogenesis. We focused on the aspects of tooth formation that are disturbed in TRPS and on potential molecular abnormalities underlying TRPS dental phenotypes. Microcomputed tomography analyses of molars were used to determine tooth size, crown shape, and mineralization of dental tissues. These analyses uncovered that disruption of one Trps1 allele is sufficient to impair mineralization of dentin in both male and female mice. Enamel mineral density was decreased only in males, while mineralization of the root dental tissues was decreased only in females. In addition, significantly smaller teeth were detected in Trps1 +/− females. Histomorphometric analyses of tooth organs showed reduced anterior-posterior diameter in Trps1 −/− mice. BrdU-incorporation assay detected reduced proliferation of mesenchymal and epithelial cells in Trps1 −/− tooth organs.Immunohistochemistry for Runx2 and Osx osteogenic transcription factors revealed changes in their spatial distribution in Trps1 −/− tooth organs and uncovered cell-type specific requirements of Trps1 for Osx expression. In conclusion, this study has demonstrated that Trps1 is a positive regulator of cell proliferation in both dental mesenchyme and epithelium, suggesting that the microdontia in TRPS is likely due to decreased cell proliferation in developing tooth organs. Furthermore, the reduced mineralization observed in Trps1 +/− mice may provide some explanation for the extensive dental caries reported in TRPS patients.