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Immunomodulatory function of all-trans retinoic acid (ATRA) has been gathering much attention for the therapy of autoimmune diseases. ATRA is a chemically unstable molecule which requires proper formulation for targeted delivery. Here we examined nanostructured lipid carrier (NLC) for the formulation of ATRA. NLC is a representative nanoparticle formulation especially suited for oral delivery. We established the preparation procedures of ATRA-containing NLC (NLC-RA) which minimizes the degradation of ATRA during the preparation process. NLC-RA thus obtained was taken up by macrophages and induced anti-inflammatory response via suppressing NF-κB signaling as well as via enhancing the production of anti-inflammatory cytokines. Moreover, NLC-RA enhanced differentiation of naïve T cells to regulatory T cells in the co-culture system with dendritic cells. These results suggest that NLC-RA is a promising alternative therapy for the autoimmune diseases especially intestinal bowel disease.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is an intractable disease of the gastrointestinal tract. Multiple environmental factors, including food ingredients, have been implicated in the development of these diseases. For example, animal fat-rich diets are predisposing factors for ulcerative colitis, whereas n-3 unsaturated fatty acids such as docosahexaenoic acid (DHA) show protective effects in experimental colitis and are negatively correlated with the incidence of ulcerative colitis and Crohn's disease. Given that DHA exhibits agonistic activity on retinoid X receptor (RXR), activation of RXR could be a therapeutic strategy for IBD. However, conventional full RXR agonists are known to show considerable adverse effects. We therefore took advantage of a partial RXR agonist, CBt-PMN, to minimize the adverse effects, and evaluated its efficacy in dextran sodium sulfate-induced colitis. Administration of CBt-PMN efficiently ameliorated the symptoms of colitis. This effect was attributed to the down-regulation of pro-inflammatory cytokines such as Tnf and Il6 in colon-infiltrating monocytes. Down-regulation of pro-inflammatory cytokines by CBt-PMN was also evident in lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDMs). Among many RXR-associated nuclear receptors, activation of peroxisome proliferator-activated receptor δ (PPARδ) and nuclear hormone receptor 77 (Nur77) suppressed cytokine production by BMDMs. These observations suggest that the activation of PPARδ/RXR and Nur77/RXR heterodimers by CBt-PMN through the permissive mechanism is responsible for diminishing the monocyte-mediated inflammatory response in the gut. Our data highlight the importance of RXR activation in the regulation of colitis.

This study deals with fibre suspension flows through cylindrical pipes. Thepresent work aims at measurements of opaque flows, which are common inindustries. Nuclear magnetic resonance imaging (NMRI) and ultrasound velocimetryprofiling (UVP) were employed as non-invasive and optic-independenttools to measure the velocity profiles. As a first experiment, a paper-pulp suspensionflow through a sudden contraction and expansion was investigated.The results show the NMRI technique can be used to measure the stronglyunsteady flow such as separated regions though the MR signal is attenuateddue to the turbulence in the flow. The flow loop had however an insufficientinlet length which caused asymmetric profiles at the test section. As a secondexperiment, a flow loop which provided fully developed flows at the test sectionwas designed. After that, the velocity profiles of rayon-fibre and micro-spheresuspension flows were measured by the NMRI and the UVP independently.In principle, these two techniques measure the different velocities of the fibresuspensionflows, i.e. the velocity of the water and the fibre. In dilute suspensionflows, where the velocities of the two phases were assumed to be thesame, the velocity profiles were in good agreement. This shows the validityof the two measurement techniques. However, it should be pointed out thatthere is a limitation of the current UVP method for highly concentrated flows.The velocity profiles obtained by the UVP at high concentrations seems notto represent physics while the NMRI is not affected by the concentrations. Itis argued that the advances of the NMRI for the measurement of the highlyconcentrated flows.