Crohn's disease and ulcerative colitis represent two distinct forms of inflammatory bowel diseases (IBD). In this paper, we discuss how immunological mechanisms contribute to the pathogenesis of IBD. Intestinal homeostasis is sustained by various kinds of cells, such as epithelial cells, lymphocytes, antigen presenting cells, and other innate immune cells. We pay special attention to intestinal CD14+ macrophages. Intestinal macrophages play a central role in the regulation of immune responses against commensal bacteria. In the physiological condition, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines. We identified a unique macrophage subset of IBD in the human intestine, which expressed both macrophage (CD14, CD33, CD68) and dendritic cell (DC) markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as interleukin (IL)-23 and tumor necrosis factor (TNF)-alpha. In addition, the CD14+ macrophages contributed to interferon (IFN)-gamma production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-gamma-positive feedback loop in IBD patients. We also discuss IFN-gamma and IL-17 production from mucosal T cells and natural killer (NK) cells. Here, we show our recent findings about the plasticity of T helper cells in colitis. Th 17 cells express T-bet, and finally lose the expression of retinoic acid-related orphan receptor (ROR)gammat, the master regulator of Th 17 cells, and are differentiated 'alternative Th 1 cells.' In addition to Th 1 cells, mucosal NK cells are also important sources of IFN-gamma. Some of our ideas may be provocative, but we hope this review paper will provide new and firm understanding of the pathogenesis of IBD.
Antigen-Presenting Cells ; Bacteria ; Child ; Child, Orphaned ; Colitis ; Colitis, Ulcerative ; Crohn Disease ; Cytokines ; Dendritic Cells ; Epithelial Cells ; Homeostasis ; Humans ; Inflammatory Bowel Diseases ; Interferons ; Interleukin-17 ; Interleukin-23 ; Interleukins ; Intestines ; Killer Cells, Natural ; Lymphocytes ; Macrophages ; Mucous Membrane ; Plastics ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Tumor Necrosis Factor-alpha

The number of patients with osteoporosis is an estimated 12,800,000 in Japan. Osteoporosis represents a risk factor for becoming bedridden, and also for increased mortality. It would thus be important to take measures to prevent non-examination and treatment interruption as their rate is high. We recruited participants at a health-supporting event for local residents at our pharmacy on April 14, 2019 and obtained consent from 40 individuals to participate in this study. At this event held by a pharmacy, we conducted bone density measurement and osteoporosis-related preventive education by pharmacists, considering the influence the event had on health-related awareness and behavior in the local residents. Knowledge of osteoporosis was higher after than before the events. Participant health and lifestyle awareness was not observed between before the event and one month after the event. However, one month after the event, several changes could be observed in the behavior of 79.4% (27/34) of the participants. Based on these results, bone density measurement and osteoporosis-related preventive education by pharmacists are suggested to increase osteoporosis-related knowledge among local residents and to promote behavior change related to healthcare and osteoporosis.

We investigated the decocting time to prepare the formulas containing unprocessed aconite root, such as shigyakuto, tsumyaku shigyakuto, and kankyobushito, which had been registered in “Shanghanlun” edited in Song Dynasty, using the weights and measures in Houhan Dynasty when the original “Shanghanlun” was regarded to have been established. Also the contents of aconitine-type diester alkaloids (ADA) eluted from unprocessed aconite root in the decoction were analyzed in time-dependent manners. As regards the modified formula for the “physically strong patients” in the texts of tsumyakushigyakuto in “Shanghanlun”, adding dried ginger was found to lead the decocting time to be shorter and the sum of ADA content in the decoction of the modified formula to increase about 20%. It was also found that the compositions of diterpene alkaloids derived from aconite root in kankyobushito decoction were highly different from those in shigyakuto decoction, containing less ADA and more aconine and hypaconine, due to the high pH of the decoction, which was the consequence of lacking glycyrrhiza in kankyobushito formula. It is suggested that the doctors in the era of “Shanghanlun” establishment may have carefully adjusted the contents of ADA in the decoctions using unprocessed aconite root by choosing co-decocted crude drugs.